bluuebunny/crossref_metadata_2025 huggingface dataset:
A venous outflow method for continuously monitoring cerebral blood flow in the rat
Authors: Morii S. , Ngai A. C. , Ko K. R. , Winn H. R.
Published: December 2017

We analyzed the retroglenoid venous outflow (VOF) technique in the rat to document the validity of this method of measuring cerebral blood flow (CBF). Stereotypic changes in CBF were obtained with VOF during hypercarbia and hypotension. O2 content of retroglenoid venous blood did not differ significantly from O2 content of blood obtained from the sagittal sinus, suggesting minimal extracerebral contamination of the retroglenoid venous blood. This lack of extracerebral contamination was further analyzed using a double tracer technique (125I-labeled serum albumin, 22Na) that quantitated minimal extracerebral contamination in the retroglenoid vein. CBF measurements were made simultaneously using microsphere and VOF methods, and excellent correlation was found between the two techniques over a wide range of CBF during normoxia, hypoxia, and normoxic hypocarbia and hypercarbia. However, a decrease in the ratio of VOF to microsphere CBF was observed during severe normoxic hypotension (mean arterial pressure = 41 +/- 4 mmHg). VOF represented 18% of total CBF as measured by microsphere method. This study indicates that the retroglenoid outflow technique in rats is a valid method of measuring CBF.
Beneficial actions of superoxide dismutase and catalase in stunned myocardium of dogs
Authors: Gross G. J. , Farber N. E. , Hardman H. F. , Warltier D. C.
Published: December 2017

Recent evidence suggests that oxygen free radicals may partially mediate irreversible ischemia-reperfusion injury in the myocardium. In the present study, the effect of a combination of two oxygen free radical scavengers, superoxide dismutase plus catalase (SOD + CAT), on the recovery of subendocardial segment function following 15 min of coronary artery occlusion followed by 3 h of reperfusion ("stunned" myocardium) was compared with a control group in barbital-anesthetized dogs. Myocardial segment shortening (%SS) in the subendocardium of nonischemic and ischemic areas was measured by sonomicrometry and regional blood flow by radioactive microspheres. SOD and CAT were infused into the left atrium 30 min before and throughout the occlusion period. Compared with the control group, %SS in the subendocardium of the ischemic region was significantly (P less than 0.05) greater in the SOD plus CAT-treated group during occlusion and throughout reperfusion. Since there were no significant differences in hemodynamics or regional myocardial blood flow between the SOD plus CAT and the control groups, these results suggest that toxic oxygen free radicals may be partially involved in the reversible ischemic injury that occurs during short periods of coronary occlusion followed by reperfusion.
Circulatory changes during spontaneous motor activity: role of arterial baroreflexes
Authors: Ludbrook J. , Potocnik S. J.
Published: December 2017

Systemic arterial pressure (SAP) and heart rate (HR) were continuously measured in rabbits during spontaneous motor activity such as postural change, exploration, grooming, and eating, and during interposed periods of inactivity within which SAP and HR were defined as basal. Six rabbits were observed for 2 h under each of 3 conditions of arterial baroreceptor afferents: all intact (B4); one carotid sinus intact (B1); all interrupted (B0). In B4, SAP and HR were above basal levels 82% of the time; in B1, 64% and 76% of the time, respectively; in B0, only 21% and 28% of the time, respectively. Supplementary experiments in another six rabbits established that the activity-associated falls of SAP in condition B0 were independent of HR, were not due to engagement of cardiac receptor reflexes, and were not abolished by autonomic ganglion blockade. We conclude that the transient rises of SAP and HR that occur during everyday activity are associated with partial or complete suppression of the reflex effects of arterial baroreceptor input, and we suggest that this is due to transient upward resetting of the arterial baroreflex.
Calcitonin gene-related peptide as potential neurotransmitter in guinea pig right atrium
Authors: Saito A. , Kimura S. , Goto K.
Published: December 2017

The potential neurotransmitter role of calcitonin gene-related peptide (CGRP) in cardioacceleratory nonadrenergic noncholinergic (NANC) nerves was examined in the guinea pig right atrium in vitro. In the presence of atropine, a muscarinic antagonist, and atenolol, a beta-adrenoceptor antagonist, transmural nerve stimulation (TNS) of the isolated right atrium caused a positive chronotropic response, which is slow in both onset and decay. This TNS-induced slow response was assumed to be mediated by NANC nerves in the right atrium since tetrodotoxin inhibited the response. Dense distribution of CGRP-like immunoreactive (CGRP-I) nerves was demonstrated in the sinus node. Exogenously applied CGRP exerted a positive chronotropic effect on the isolated right atrium in a dose-dependent manner. Both CGRP-I nerves and NANC response induced by TNS were not affected by surgical sympathectomy and reserpine pretreatment but were abolished by the pretreatment of animals with capsaicin. The results suggest that CGRP is the neurotransmitter of cardioacceleratory NANC nerves in the right atrium of the guinea pig.
Mechanism of skeletal muscle underperfusion in a dog model of low-output heart failure
Authors: Wilson J. R. , Falcone R. , Ferraro N. , Egler J.
Published: December 2017

To investigate the mechanism responsible for underperfusion of working skeletal muscle in heart failure, we measured systemic and femoral bed hemodynamics during treadmill exercise and gracilis muscle resistance during contraction frequencies of 1-9 Hz in 8 dogs ventricularly paced at 260 beats/min for 3 wk to induce heart failure (HF) and in 9 control dogs. At peak treadmill exercise (4 mph, 10%), HF dogs had reduced cardiac outputs (control: 297 +/- 42 vs. HF: 212 +/- 16 ml X min-1 X kg-1) and femoral bed flows (control: 352 +/- 112 vs. HF: 229 +/- 95 ml/min) and elevated arterial lactates [control: 1.7 +/- 0.7 vs. HF: 4.1 +/- 0.7 mM (all P less than 0.04)], consistent with skeletal muscle underperfusion. This muscle underperfusion was associated with reduced mean arteriovenous pressure gradients [control: 119 +/- 12 vs. HF: 91 +/- 9 mmHg (P less than 0.001)] but with normal systemic vascular [control: 21 +/- 6 vs. HF: 23 +/- 5 U (P = NS)] and femoral bed resistances [control: 3.5 +/- 1.6 vs. HF: 4.4 +/- 2.3 X 10(2) U (P = NS)]. Both groups also had similar gracilis muscle minimal resistance during exercise (control: 2.0 +/- 1.1 vs. HF: 1.9 +/- 0.9 X 10(3) U/100 g) and following maximal vasodilation (control: 2.0 +/- 1.0 vs. HF: 2.1 +/- 1.0 X 10(3) U/100 g). These results suggest that 1) short-term rapid ventricular pacing in the dog produces a model of low output HF resembling HF in humans, and 2) skeletal muscle underperfusion in this model is due to a reduced muscle arteriovenous pressure gradient and not to impaired skeletal muscle arteriolar vasodilation.
Left ventricular function during lethal and sublethal endotoxemia in swine
Authors: Goldfarb R. D. , Nightingale L. M. , Kish P. , Weber P. B. , Loegering D. J.
Published: December 2017

Our previous studies suggested that after a median lethal dose (LD50) of endotoxin, cardiac contractility was depressed in nonsurviving dogs. The canine cardiovascular system is unlike humans in that dogs have a hepatic vein sphincter that is susceptible to adrenergic stimulation capable of raising hepatic and splanchnic venous pressures. We retested the hypothesis that lethality after endotoxin administration is associated with cardiac contractile depression in pigs, because the hepatic circulation in this species is similar to that of humans. We compared cardiac mechanical function of pigs administered a high dose (250 micrograms/kg) or a low dose (100 micrograms/kg) endotoxin by use of the slope of the end-systolic pressure-diameter relationship (ESPDR) as well as other measurements of cardiac performance. In all the pigs administered a high dose, ESPDR demonstrated a marked, time-dependent depression, whereas we observed no significant ESPDR changes after low endotoxin doses. The other cardiodynamic variables were uninterpretable, due to the significant changes in heart rate, end-diastolic diameter (preload), and aortic diastolic pressure (afterload). Plasma myocardial depressant factor activity accumulated in all endotoxin-administered animals, tending to be greater in the high-dose group. In this group, both subendocardial blood flow and global function were depressed, whereas pigs administered the low dose of endotoxin demonstrated slight, but nonsignificant, increases in flow and function. These observations indicate that myocardial contractile depression is associated with a lethal outcome to high doses of endotoxin. One possible mechanism for this loss of contractile function may be a relative hypoperfusion of the subendocardium.
Insulin reversal of biochemical changes in hearts from diabetic rats
Authors: Bhimji S. , Godin D. V. , McNeill J. H.
Published: December 2017

Reversal of myocardial biochemical changes with insulin treatment (4 and 8 wk) was studied in 8 and 12 wk streptozotocin (STZ)-diabetic rats. STZ-induced diabetes was characterized by elevations in blood glucose, serum cholesterol, and triglycerides and depressed serum insulin levels. Insulin treatment for 4 and 8 wk completely restored the serum alterations to control values. The polyuria, polydipsia, and polyphagia were also markedly diminished by the insulin treatment. Diabetic rats had pronounced decreases in body, heart, and left ventricular weights, all of which were completely reversed by the insulin treatment. Hydroxyproline accumulation in diabetic rat hearts was only reversed by the 8-wk and not by the 4-wk insulin treatment. STZ produced a significant depletion of left ventricular magnesium content as well as depression of K+-stimulated sarcoplasmic reticulum and myofibrillar ATPase activities. Both the 4- and 8-wk insulin treatment produced a complete recovery of the myocardial magnesium content. No significant changes in sarcolemmal Na+-K+-ATPase and K+-stimulated p-nitrophenyl phosphatase activities were observed in diabetic animals compared with control. The decreased latency of the lysosomal hydrolase, N-acetyl-beta-glucosaminidase, and the increased collagen deposition observed in the diabetic hearts were only partially reversed by the 4-wk insulin treatment, but completely reversed by the 8-wk treatment period.
Direct cardiac effects of vasopressin and their reversal by a vascular antagonist
Authors: Boyle W. A. , Segel L. D.
Published: December 2017

We studied the direct cardiac effects of arginine vasopressin (AVP) by use of an isolated working rat heart model perfused with Krebs-Henseleit medium. At a concentration of 878 +/- 15 pg/ml, AVP produced significant (P less than 0.05) decreases in coronary flow (-31 +/- 2%); myocardial O2 consumption (-12 +/- 2%); left ventricular peak systolic pressure (-5 +/- 1%); dP/dtmax (-7 +/- 1%); -dP/dtmax (-6 +/- 3%); peak aortic flow rate (-5 +/- 1%); stroke work (-3 +/- 1%); peak power (-8 +/- 1%); and total output (-3 +/- 1%). Aortic output increased significantly (+7 +/- 1%) as did arteriovenous O2 difference (+108 +/- 14 mmHg); left ventricular end-diastolic pressure (+0.4 +/- 0.1 mmHg); efficiency (+1.5 +/- 0.4%); and rate of lactate release (+1.27 +/- 0.21 nmol/ml perfusate/min). Dose-response relationships were studied at 9 +/- 1, 25 +/- 1, 75 +/- 3, 303 +/- 15, and 817 +/- 42 pg AVP/ml. Significant dose-dependent depression of coronary flow occurred at the three highest AVP concentrations; cardiac function was significantly depressed at the highest dose. The AVP analogue d(CH2)5[Tyr(Me)]AVP (20 ng/ml) completely reversed the cardiac effects attributed to AVP. The data indicate that AVP is a potent direct coronary constrictor that produces myocardial ischemia and decreased contractile function at AVP concentrations that are observed in some pathophysiologic states.(ABSTRACT TRUNCATED AT 250 WORDS)
Absence of sustained hypertension in sinoaortic-denervated rabbits
Authors: Saito M. , Terui N. , Numao Y. , Kumada M.
Published: December 2017

In 21 conscious unrestrained rabbits, arterial pressure was continuously recorded up to 11 wk by an indwelling catheter placed in the thoracic aorta. The average and standard deviation of the 24-h mean arterial pressure (MAP) were calculated and compared before and after sinoaortic denervation, sham operation, or cervical sympathectomy. At the time of sinoaortic denervation, the cervical sympathetic nerve was always disrupted bilaterally to remove possible arterial barosensory afferents contained in it. Subsequent to sinoaortic denervation performed on 12 rabbits, the average 24-h MAP was initially elevated but invariably returned to the predenervation level in 5-36 days (average 14 days). Meanwhile, the standard deviation remained elevated in all but one animal. In five sham-operated or four cervical-sympathectomized animals, neither the average 24-h MAP nor the standard deviation was significantly altered from that of controls. Our results are consistent with the view that the arterial baroreceptor reflex by itself does not play a critical role in determining the long-term level of arterial pressure.
Effects of verapamil on regional myocardial diastolic function in pacing-induced ischemia in dogs
Authors: Bourdillon P. D. , Paulus W. J. , Serizawa T. , Grossman W.
Published: December 2017

The upward shift in the left ventricular diastolic pressure-volume relationship during pacing-induced angina may be related to increased cytosolic calcium availability with persistent contractile element interaction in diastole. To assess the influence of calcium channel blockade on these changes in diastolic function, we studied the effects of verapamil in dogs with 90% stenoses of the left anterior descending and circumflex coronary arteries. Ultrasonic crystals were implanted in the myocardium to monitor anterior wall and lateral wall segment length. Left ventricular pressure was measured with a micromanometer catheter. The left atrium was paced at a rate 1.5 times that of the resting heart rate for 3 min. An upward shift of the left ventricular diastolic pressure-segment length relationship developed after pacing tachycardia, with a rise in the left ventricular end-diastolic pressure (LVEDP) from 4.7 +/- 1.2 to 14.3 +/- 2.2 mmHg (P less than 0.01, n = 13), and pressure was higher at any segment length throughout diastole. Increases in end-diastolic segment length were small (12.3 +/- 1.9 to 12.7 +/- 2.0 mm for the anterior wall, P less than 0.05; 15.1 +/- 1.4 to 16.4 +/- 1.5 mm for the lateral wall, P less than 0.01). Pretreatment with verapamil (0.08 mg/kg iv) did not reduce this upward shift: LVEDP rose from 6 +/- 1 to 16 +/- 1 mmHg (P less than 0.01, n = 7) and there were similar small increases in end-diastolic segment length.(ABSTRACT TRUNCATED AT 250 WORDS)
Microtubule reorganization is related to rate of heart myocyte hypertrophy in rat
Authors: Samuel J. L. , Marotte F. , Delcayre C. , Rappaport L.
Published: December 2017

Since stimulation of heart hypertrophy by pressure overload was previously shown to be accompanied by a densification of microtubule network in rat heart myocytes, we verified that similar process occurred during postnatal growth in euthyroid rats and in hypothyroid rats whose growth was stimulated by 4 micrograms/day L-thyroxine (T4). For this purpose, tubulin, the constituent protein of microtubules, was immunolabeled in myocytes isolated at various times after birth. Myocyte hypertrophy was evaluated by myocyte size, the number of nuclei per cell and isomyosin expression. In hypothyroid rats, the microtubule network, which was underdeveloped, was most dense around the nucleus. During the phase of fast myocyte hypertrophy observed in euthyroid rats during late postnatal development and in hypothyroid rats after T4 administration, transient microtubule densification occurred in a myocyte subpopulation in which size was mainly determined by the rate of myocyte hypertrophy. The densification process and its kinetics resembled those observed when heart hypertrophy was induced by pressure overload. It is concluded that in rat heart myocytes undergoing hypertrophy, microtubule densification might be related to fast sarcomerogenesis, whether the stimulus is mechanical (e.g., pressure overload) or hormonal (e.g., T4).
Inorganic phosphate inhibits sympathetic neurotransmission in canine saphenous veins
Authors: Edoute Y. , Vanhoutte P. M. , Shepherd J. T.
Published: December 2017

Inorganic phosphate has been proposed as the initiator of metabolic vasodilatation in active skeletal muscle. The present study was primarily designed to determine if this substance has an inhibitory effect on adrenergic neurotransmission. Rings of canine saphenous veins were suspended for isometric tension recording in organ chambers. A comparison was made of the ability of inorganic phosphate (3 to 14 mM) to relax rings contracted to the same degree by electrical stimulation, exogenous norepinephrine, and prostaglandin F2 alpha. The relaxation during electrical stimulation was significantly greater at all concentrations of phosphate. In strips of saphenous veins previously incubated with [3H]norepinephrine, the depression of the contractile response caused by phosphate during electrical stimulation was accompanied by a significant reduction in the overflow of labeled neurotransmitter. Thus inorganic phosphate inhibits sympathetic neurotransmission and hence may have a key role in the sympatholysis in the active skeletal muscles during exercise. By contrast, in this preparation, it has a modest direct relaxing action on the vascular smooth muscle.
Microvascular hematocrit and red cell flux in rat cremaster muscle
Authors: House S. D. , Lipowsky H. H.
Published: December 2017

The arteriovenous distributions of volumetric flow (Q), microvessel hematocrit (Hctmicro), and estimates of red cell volumetric flux (QRBC) were obtained under control conditions in rat cremaster muscle. The results demonstrate a monotonic fall in the ratio of Hctmicro/Hctsystemic from 0.86 in 70-microns arterioles to 0.48 in capillaries followed by a subsequent rise to 0.79 in 98-microns venules. To assess the roles of Hctmicro and Q in red blood cell delivery following a period of reduced oxygen transport, tissue ischemia was produced by occluding the first order arteriole. During the occlusion, arteriolar and large venular hematocrits fell 15–30%, whereas small venular hematocrits increased 24%. After release of the occlusion, a reactive hyperemia ensued with Q, QRBC, and QHctmicro increasing significantly above control values in arterioles, capillaries, and venules. All Hctmicro returned to their control values within 10 s following resumption of flow. Based on the relationship between blood viscosity and Hctmicro, at low shear rate, these transient alterations in Hctmicro were estimated to have a profound effect on blood viscosity, and hence the resistance to blood flow. Such changes may affect recovery from an ischemic episode, although not adversely affecting the oxygen-carrying capacity of blood and convective transport of oxygen.
Effects of ACE inhibition and beta-blockade on skeletal muscle fiber types in dogs with moderate heart failure
Authors: Sabbah H. N. , Shimoyama H. , Sharov V. G. , Kono T. , Gupta R. C. , Lesch M. , Levine T. B. , Goldstein S.
Published: December 2017

The proportion of slow-twitch, fatigue-resistant type 1 skeletal muscle (SM) fibers is often reduced in heart failure (HF), while the proportion of fatigue-sensitive type-II fibers increases. This maladaptation may be partially responsible for the exercise intolerance that characterize HF. In this study, we examined the effects of early monotherapy with the angiotensin-converting enzyme inhibor, enalapril, and the beta-blocker, metoprolol, on SM fiber type composition in 18 dogs with moderate HF produced by intracoronary microembolizations. HF dogs were randomized to 3 mo therapy with enalapril (10 mg twice daily), metoprolol (25 mg twice daily), or no treatment. Triceps muscle biopsies were obtained at baseline, before randomization, and at the end of 30 mo of therapy. Type I and type II SM fibers were differentiated by myofibrillar adenosinetriphosphatase (pH 9.4). In untreated dogs, the proportion of type I fibers was 27 +/- 1% before randomization and decreased to 23 +/- 1% (P < 0.05) at the end of 3 mo of follow up. In dogs treated with enalapril or metoprolol, the proportion of type I fibers was 30 +/- 4 and 28 +/- 2% before randomization and 33 +/- 4 and 33 +/- 1%, respectively, after 3 mo of therapy. In conclusion, in dogs with moderate HF, early therapy with enalapril or metoprolol prevents the progressive decline in the proportion of type I SM fibers.
Effects of adenosine analogues on tension and cytosolic Ca2+ in porcine coronary artery
Authors: Olanrewaju H. A. , Mustafa S. J.
Published: December 2017

This study evaluates the relaxing effects of adenosine analogues in relation to intracellular free Ca2+ concentration ([Ca2+]i) in porcine coronary artery. Changes in muscle tension and [Ca2+]i were measured simultaneously using the fluorescent Ca2+ indicator, fura 2-acetoxymethyl ester. The ratio of fluorescence due to excitation at 340 nm to that at 380 nm reflects [Ca2+]i. Increased tension of the porcine coronary artery contracted with prostaglandin F2 alpha (PGF2 alpha, 20 microM) was accompanied by increased [Ca2+]i. The adenosine analogues, N6-cyclopentyladenosine (CPA), 2-chloroadenosine (CAD), and 2-[m-(carboxyethyl)-phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS-22988) produced a concentration-dependent (10(-8)-10(-4) M) reduction of [Ca2+]i and tension with a maximum relaxation of approximately 96% and a [Ca2+]i decrease of 88% at a concentration of 10(-4) M. The order of potency for relaxation was CAD > CGS-22988 = CPA. Adenosine receptor antagonists (8-phenyltheophylline, 10(-6) M; CGS-15943, 10(-5) M) shifted the agonist-mediated relaxation and [Ca2+]i curve to the right in a parallel fashion. In Ca(2+)-free buffer, PGF2 alpha (20 microM)-induced contraction was significantly reduced (75%). PGF2 alpha also caused a transient increase in [Ca2+]i that later was reduced below the resting level. The order of potency for relaxation for adenosine analogues in Ca(2+)-free buffer was found to be CAD = CGS-22988 > CPA. All curves were shifted to the right in the presence of receptor antagonists. These results indicate that adenosine receptor-mediated changes in [Ca2+]i and relaxation in porcine coronary smooth muscle are at least partly independent of extracellular Ca2+.
Comparative cardioprotective effects of cromakalim and diltiazem in ischemic hypertrophied rat hearts
Authors: Grover G. J. , Dzwonczyk S. , Monticello T. M.
Published: December 2017

Previous studies have indicated that alterations in cardiac ATP-sensitive potassium channels (KATP) can occur with cardiac hypertrophy. The goal of this study was to determine the effect of cardiac hypertrophy in spontaneously hypertensive rats (SHR) on the response to the cardioprotective agents diltiazem and cromakalim. Isolated rat hearts from 14-wk-old SHR, normotensive heterozygote Wistar-Kyoto (WKY), and Sprague-Dawley (SD) strains were subjected to 25 min of global ischemia and 30 min of reperfusion in the presence of vehicle (3-30 microM cromakalim or 0.1-1.0 microM diltiazem). SHR had heart weight-to-body weight ratios 40-50% greater than age-matched SD or WKY. Both diltiazem and cromakalim increased reperfusion contractile function in a concentration-dependent manner in SD rats as previously reported. Cromakalim and diltiazem caused similar improvements in reperfusion function in WKY rats and SHR. Cumulative lactate dehydrogenase (LDH) release during reperfusion was similar for vehicle-treated SD, WKY, or SHR hearts. LDH release was significantly attenuated by cromakalim and dilitiazem at all concentrations tested in SD and WKY hearts, whereas LDH release was not attenuated in SHR hearts by any concentration of cromakalim or diltiazem tested. Morphological assessment of hearts by light microscopy indicated that the severity and distribution of myocardial lesions were not affected by cromakalim in SHR hearts, compared with vehicle-treated SHR, supporting the LDH data. These results suggest that in SHR hearts, cromakalim and dilitiazan may exert much of their cardioprotective effects on the population of myocytes that are not irreversibly damaged.
1,25(OH)2D3 modulates intracellular Ca2+ and force generation in resistance arteries
Authors: Bian K. , Ishibashi K. , Bukoski R. D.
Published: December 2017

The mechanism by which 1 alpha,25-dihydroxycholecalciferol [1,25(OH)2D3] enhances smooth muscle force generation was examined. Rats were injected on three mornings with 1,25(OH)2D3 (35 ng/100 g) or vehicle, and on the fourth morning mesenteric resistance arteries were isolated and used for simultaneous measurement of intracellular Ca2+ and force or myosin light chain phosphorylation. 1,25(OH)2D3 did not affect media thickness or wall-to-lumen ratio, but it increased basal intracellular Ca2+ (vehicle = 49.2 +/- 2.2 nM vs. 1,25(OH)2D3 = 65.9 +/- 4.0 nM, P < 0.05, n = 24-26 rats). 1,25(OH)2D3 enhanced the active stress and intracellular Ca2+ responses to increasing doses of norepinephrine, and the increases were normalized by verapamil (10 microM). In a second group of animals, 1,25(OH)2D3 significantly increased both basal intracellular Ca2+ and light chain phosphorylation and the active stress and Ca2+ mobilization responses to norepinephrine (10 microM). The hormone did not affect peak or steady-state light chain phosphorylation. Myofilament Ca2+ sensitivity, determined during stimulation with 2 microM norepinephrine, was depressed in vessels isolated from rats treated with 1,25(OH)2D3 [vehicle Ca2+ 50% effective dose (ED50) = 82.7 +/- 3.8 nM vs. 1,25(OH)2D3 = 104.8 +/- 4.9 nM, P = 0.002]. We conclude that 1,25(OH)2D3 enhances resistance artery force generation by altering smooth muscle Ca2+ homeostasis, with effects on basal and verapamil-sensitive, agonist-induced Ca2+ mobilization.
CGP-48506 increases contractility of ventricular myocytes and myofilaments by effects on actin-myosin reaction
Authors: Wolska B. M. , Kitada Y. , Palmiter K. A. , Westfall M. V. , Johnson M. D. , Solaro R. J.
Published: December 2017

We measured the effects of the benzodiazocine derivative, CGP-48506 (5-methyl-6-phenyl-1,3,5,6-tetrahydro-3,6-methano-1, 5-benzodiazocine-2,4-dione), on contraction of intact myocytes and permeabilized fibers of rat ventricular muscle. CGP-48506 is unique in that it is able to sensitize cardiac myofilaments to Ca2+, but unlike all other agents in this class, it is not an inhibitor of type III phosphodiesterase. When added to isolated intact myocytes, CGP-48506 significantly increased the amplitude of cell shortening with little or no change in the Ca2+ transient, as determined by the fluorescence ratio of fura 2. The late phase of the relation between fura 2 ratio and cell length was shifted to the left in the presence of CGP-48506. CGP-48506 also induced a relatively small decrease in diastolic length. However, compared with the thiadiazinone EMD-57033, CGP-48506 had a much smaller effect on diastolic length at concentrations in which there was a bigger inotropic effect. When added to solutions bathing detergent-extracted (skinned) fiber bundles, CGP-48506 increased maximum force. CGP-48506 also increased submaximal force and shifted the pGa-force relation to the left. However, compared with EMD-57033, there was less of an effect of CGP-48506 on force at relatively high pCa values. CGP-48506 did not alter Ca2+ binding to myofilament troponin C. CGP-48506 was able to reverse inhibition of contraction induced by butanedione monoxime both in intact cells and in skinned fiber bundles. Our results indicate that CGP-48506, like EMD-57033, is a positive inotropic agent working through a direct effect downstream from troponin C. CGP-48506, however, appears to have a unique mechanism resulting in less effect on diastolic function.
Transport in lymphatic capillaries. II. Microscopic velocity measurement with fluorescence photobleaching
Authors: Berk D. A. , Swartz M. A. , Leu A. J. , Jain R. K.
Published: December 2017

Despite its relevance to the physiology of lymph formation and propulsion, the instantaneous flow velocity in single lymphatic capillaries has not been measured to date. The method of fluorescence recovery after photobleaching (FRAP) was adapted for this purpose and used to characterize flow in the lymphatic capillaries in tail skin of anesthetized mice during a constant-pressure intradermal injection of fluorescein isothiocyanate-dextran (mol wt 2 x 10(6). The median lymph flow velocity was 4.7 microns/s, and the velocity magnitude ranged from 0 to 29 microns/s. The direction of flow was generally proximal, but stasis and backflow toward the site of injection was also detected. Evidence for oscillatory flow was detected in some FRAP experiments, and in separate experiments a periodicity of approximately 120 min-1, directly correlated to respiration frequency, was measured by tracking the motion of fluorescent latex microspheres (1 micron diam) introduced into the lymphatic capillary network. The velocity magnitude showed a correlation with duration of infusion but not with distance from injection site. It is speculated that the temporal decay of mean velocity magnitude could be related to the relaxation of local pressure gradients as partially collapsed vessels expand during the infusion.
CHANGES IN THE EXCRETION OF CARBON DIOXIDE RESULTING FROM BICYCLING
Authors: Higley G. O. , Bowen W. P.
Published: December 2017

In Figure 6, p. 329, of Volume XII, the ordinates for carbon dioxide beginning at the base line are:

grams 0.7

1.4

2.1

2.8

3.5

The excretion per minute before the beginning of work was 0.42 gram.
CONCERNING THE RELATIONSHIP BETWEEN THE STRENGTH OF ACIDS AND THEIR CAPACITY TO PRESERVE NEUTRALITY
Authors: Henderson Lawrence J.
Published: December 2017

On page 177, line 5, the equation should read

(See PDF)
ELECTRICAL STUDIES IN MAMMALIAN REFLEXES
Authors: Forbes Alexander , Gregg Alan
Published: December 2017

In the December, 1915, issue of this Journal (vol. xxxix, no. 2) a number of the figures accompanying the article by Forbes and Gregg entitled: "Electrical Studies in Mammalian Reflexes. II. The Correlation Between Strength of Stimuli and the Direct and Reflex Nerve Response," were, through a misunderstanding, printed on the wrong kind of paper and failed to show many details which appeared in the original photographs. These figures are, therefore, reproduced for reference.

(See PDF)
RHEOTROPIC RESPONSES OF EPINEPHELUS STRIATUS BLOCH
Authors: Jordan Hovey
Published: December 2017

(Insert opposite page 444, Volume xliii, 1917)

The sentence (page 444, paragraph 2) beginning: "It should be noted, how ever," should be interchanged with the first part of a sentence on page 45 (paragraph 1), viz., with "It should be noted that . . . . the position were posterior."
ON THE HEAT LIBERATED BY THE BEATING HEART
Authors: Snyder Charles D.
Published: December 2017

[To be inserted between pp. 158 and 159, Vol. xlvii.]

Page 159, line 15, for "0.0007" read ".0018,"

Page 160, line 4, for the sentence beginning here read, "The heat produced was .83 x .00156, or .0013 calorie per gram ventricle."

Page 163, line 19, for "0.00048, 0.00052 and 0.00073", read ".0011, .0013 and .0018." line 21, for "0.00062" read, ".00155" line 30, for "1.3" and "1.67" read "3.2" and "4.5."

Page 164, last line, for "well within" read "nearer the greater of."
INSENSIBLE PERSPIRATION AND THE GALVANIC SKIN REFLEX
Authors: Freeman G. L. , Darrow Chester W.
Published: December 2017

On last line of table 1, page 58 (February, 1935), Volume 111, read 91, 74, 75, instead of 97, 94, 95.
CHANGES IN THE CORONARY CIRCULATION FOLLOWING INCREASED AORTIC PRESSURE, AUGMENTED CARDIAC OUTPUT, ISCHEMIA AND VALVE LESIONS
Authors: Green Harold D. , Gregg Donald E.
Published: December 2017

Volume 130. On page 128, table 1, column headed "Total flow—Diastole", last line: change 0.56 to 0.056.

On page 129, line 13, first word: Change increases to decreases.
THE EFFECT OF EPINEPHRINE ON THE POTASSIUM BALANCE OF THE HIND LIMBS OF THE FROG
Authors: Stickney J. Clifford
Published: December 2017

Volume 132, page 10, line 32, KCl, 0.650 per cent should read KCl, 0.0450 per cent.
ADRENALINE ESTER
Authors: Richter Derek , MacIntosh F. C.
Published: December 2017

Amer. J. Physiol. 135: no. 1, p. 1, 1941. Adrenaline Ester. Derek Richter and F. C. MacIntosh

(1) p. 2, line 19. For 1 mgm. adrenaline read 1 µgm. adrenaline.

(2) p. 3, line 1. For 1 mgm. adrenaline read 1 µgm. adrenaline.

(3) line 6. For 1 mgm. adrenaline read 1 µgm. adrenaline.

(4) line 7. For 25 mgm./ml. read 25 µgm./ml.

(5) p. 4, line 1. For 6.1 mgm. adrenaline/ml. read 6.1 µgm., etc.

(6) line 2. For 1.5 mgm. adrenaline/ml. read 1.5 µgm., etc.

(7) Fig. 1, p. 2, line 4 of legend. For 2 mgm. adrenaline read 2 µgm. adrenaline.

(8) Fig. 2, p. 3, line 2 of legend. For 25 mgm. adrenaline read 25 µgm. adrenaline.

Contexts of above:

(1) The cat showed a clear blood pressure rise with 1 mgm. adrenaline.

(2) The nictitating membrane and intestine showed a definite response to 1 mgm. adrenaline.

(3, 4) The response with unhydrolysed urine after taking adrenaline was only slight and corresponded to less than 1 mgm./ml. adrenaline, while solution (A) containing the hydrolysed ester gave responses corresponding to 25 mgm./ml. adrenaline.

(5, 6) ... the amount found after taking 10 mgm. adrenaline corresponded to 6.1 mgm./ ml. in the urine collected in the first 4 hours and 1.5 mgm./ml. during the subsequent 5 hours.

(7) E, Response to 2 mgm. adrenaline.

(8) A, 25 mgm. adrenaline.
Influence of potassium on renal ammonia production
Authors: Tannen RL , McGill J
Published: December 2017

The influence of potassium homeostasis on ammonia production was investigated with both cortical and medullary slices from rat kidney. Renal cortical slices from rats depleted of potassium by dietary restriction produced 31% more NH3 than slices from pair-fed controls. A high-potassium diet for 1 wk diminished ammonia production in cortical slices by 5% in comparison with rats pair fed a normal diet (161 vs. 169 mumol/90 min per g wet wt; P less than 0.05). Pair feeding did not introduce an experimental artifact, since animals ingesting similar K+ diets showed no difference in NH3 production. In contrast to cortex, NH3 production by outer medullary slices from K+-depleted animals was similar to pair-fed controls. Medulla from potassium-loaded rats exhibited an impressive inhibition in NH3 production averaging 36%. These striking differences between cortex and medulla suggest that specific alterations in potassium homeostasis may influence NH3 production selectively at different tubular sites. In vitro manipulation of K+ homeostasis produced by varying bathing media K+ from 0 to 144 mM, with concomitant changes in intracellular K+ from 30 to 130 mM, had no detectable influence on NH3 production by cortical slices. Hence altered cortical ammoniagenesis is not the direct result of acute changes in extracellular or intracellular cortical fluid K+ or in the transcellular gradient for K+. Although the specific cellular mechanisms whereby K+ alters ammoniagenesis remains undefined, the observation that K+ loading diminishes while K+ depletion enhances NH3 production supports the supposition that K+ and NH3 are linked in a physiologic control system.
Intracellular potassium activities in Amphiuma small intestine
Authors: White JF
Published: December 2017

Intracellular potassium activity (aKi) has been determined in absorptive cells lining the villi of isolated, stripped proximal segments of Amphiuma small intestine. With single-barreled liquid ion-exchanger microelectrodes aKi = 41.6 +/- 1.5 mM in normal chloride buffer; with double-barreled microelectrodes constructed by a new method aKi = 38.5 +/- 2.4 mM. Also, by the latter approach aKi = 41.1 +/- 2.1 mM in buffer in which potassium was elevated to 5 meq/liter and aKi = 44.2 +/- 1.3 mM in sulfate buffer with the same bath potassium concentration. Since the calculated potassium equilibrium potential exceeds the membrane potential this ion is accumulated by the intestinal absorptive cell. A major portion of cellular potassium is bound or compartmentalized since the intracellular potassium activity coefficient is very low. A layer exists near the villi in which the potassium activity exceeds that in the bath buffer solution.
Free-feeding patterns of rats in response to changes in environmental temperature
Authors: Leung PM , Horwitz BA
Published: December 2017

Four adult Sprague-Dawley rats (430-450 g), maintained on a 12:12 h dark/light cycle and 15% casein diet, were exposed to cold (5 degrees C) for 77 days and then transferred back to 24 degrees C. Throughout thisperiod, the feeding patterns of the rats were measured with recording balances. Cold exposure caused an immediate reduction in nocturnal meal frequency that remained low during the cold exposure. In contrast, diurnal meal frequency was unaltered. Average nocturnal meal size, which did not significantly increase before 8 days of cold, reached a plateau in 2 wk, whereas the average diurnal meal size did not significantly change until late in the exposure period. "Warm" (24 degrees C) reentry elicited an abrupt increase in nocturnal meal frequency and a reduction in average nocturnal as well as diurnal meal size. It thus appears that even in the face of a sudden increase in energy expenditure resulting from cold exposure, adult rats do not immediately adjust their daily food intake. On the other hand, the adaptive hyperphagic response occurring after cold acclimation is abolished when the energy demand is eliminated, i.e., when the animals are removed from the cold.
Effect of angiotensin II antagonist infusion on autoregulation of renal blood flow
Authors: Abe Y , Kishimoto T , Yamamoto K
Published: December 2017

The role of the renin-angiotensin system in the autoregulation of renal blood flow was examined in the anesthetized dog. The angiotensin II antagonist, [1-sarcosine, 8-isoleucine]angiotensin II, was continuously infused into the renal artery at rates of 1 and 3 mug/min, and renin secretion rate and intrarenal distribution of blood flow as well as total renal blood flow were measured during acute reductions in renal perfusion pressure within and below the range of autoregulation. Renal autoregulation and redistribution of blood flow by pressure reduction were not disturbed by the angiotensin II antagonist. This result does not provide any evidence for a primary role of the renin-angiotensin system in renal autoregulation. Redistribution of blood flow by pressure reduction occurred independently of the renin-angiotensin system. It might depend on the differences in the resting tone among the zones.
Renin-angiotensin system in spontaneously hypertensive rats
Authors: Shiono K , Sokabe H
Published: December 2017

Plasma and kidney renin activities (PRA, KRA) were determined in male spontaneously hypertensive rats (SHR), the inbred strain of F27-30. Blood samples of 0.5 ml for PRA determination were obtained through a cannula inserted into the abdominal aorta without anesthesia to minimize renin release from the kidney. The PRA was 30 wk. The KRA of SHR at age 10, 20, and 30 wk was also lower, confirming a previous report. At 5 wk of age, KRA was slightly higher than that of normal controls. At 50 wk of age, PRA and KRA were significantly lower in SHR (F25) from a random-bred colony than in normal Donryu rats. It is suggested that the renin-angiotensin system is suppressed in SHR as a compensatory reaction against blood pressure elevation.
Series elasticity of urinary bladder smooth muscle
Authors: Alexander RS
Published: December 2017

Loops of rat bladder were stretched between pins in vitro, supported by a clamp that could be suddenly shortened by activation of a solenoid to achieve a quick release of tension. The series elasticity measured in this fashion was found to follow an exponential course and to be modified by the rate of release, indicating a minor viscous component. Tissue length decreased and series elastic stiffness appeared to increase with muscle contraction, but no alteration in series elasticity was evident when the data were related to the tension existing in the tissue at the moment of quick release. Inactivation of the contractile system by removing calcium ion with ethylene glycol-bis-(beta-aminoethylether)-N,N'-tetraacetate (EGTA) similarly did not alter series elasticity when it was related to the tension existing in the tissue. Series elasticity during the stress relaxation following a stretch, and during the contracting and relaxing phases of rhythmic contractions, was also determined by tissue tension. The conclusion drawn is that contractile cross bridges do not contribute to the series elasticity measured in bladder tissue.
Effect of parathyroid hormone on renal tubular permeability
Authors: Lorentz WB
Published: December 2017

The effect of parathyroid hormone (PTH) on renal tubular permeability has been studied utilizing micropuncture techniques in the rat kidney. After microinjection into superificial nephrons during control conditions, inulin (98.8 +/- 2.7%) and mannitol (97.2 +/- 2.4%) recovery from the experimental kidney was essentially complete. During intravenous infusion of PTH, inulin (99.3 +/- 2.9%) recovery was again complete. Mannitol recovery decreased signficantly after both early-proximal (84.7 +/- 5.8%, P less than 0.001) and late-proximal (89.7 +/- 2.8%, P less than 0.001) injections. There was no loss of either mannitol or inulin following distal tubular injection. Late-proximal TF/P inulin ratios during control conditions were 2.10 +/- 0.20 and decreased insignificantly to 1.99 +/- 0.21 during PTH infusion. Late-proximal TF/P mannitol rations were 2.09 +/- 0.21 during control periods and during PTH infusion decreased significantly to 1.78 +/- 0.19 (P less than 0.001). These results indicate that PTH induces a change in proximal tubular permeability to a usually impermeable nonelectrolyte, mannitol. The effects of PTH on proximal tubular transport could be partially explained by this alteration in permeability, which would increase passive backflux of actively transported species and decrease net transport while having no effect on active transport.
Prostaglandin E release in the dog: effect of sodium
Authors: Terashima R , Anderson FL , Jubiz W
Published: December 2017

Renal arterial injections (20 ml) of 4 M NaCl in 8 dogs and of 0.5 M NaCl in two dogs were followed by significant but delayed increases over 60 min in renal venous prostaglandin E (PGE) concentrations as measured by radioimmunoassay. Perfusion pressure increased significantly only at 5 min but plasma sodium concentration remained above base line for 60 min. In two dogs in which renal artery blood flow was maintained at a constant rate, comparable increases in PGE concentrations were observed. Injections of 1 M mannitol in three dogs and 5% dextrose in water in two dogs did not result in significant changes in PGE concentrations. In four dogs, administration of 50 mg indomethacin 15 min prior to injection of 20 ml of 4 M NaCl abolished the changes of PGE concentration. Sodium appears to have an effect on stimulation of PGE release by the canine kidney. This phenomenon may be of physiologic significance.
Metabolism of ketone bodies by ovine brain in vivo
Authors: Kammula RG
Published: December 2017

Ketosis was produced by intravenous infusion (5 mmol/kg per h) of [3-14C]acetoacetate (sp act 0.5 muCi/mmol) into fed and 7-day-fasted sheep. Changes in arterial and sagittal sinus blood samples. During acetoacetate infusion, there was a significant increase in ketone body uptake (P less than 0.001) and conversion to 14CO2 in both fed and fasted sheep. Changes in arterial concentrations and cerebral removal of various metabolites were investigated by simultaneous collection of arterial and sagittal sinus blood samples. During acetoacetate infusion, there was a significant increase in ketone body uptake (P less than 0.001) and conversion to 14CO2 in both fed and fasted sheep when compared to control periods (saline infusion). The percent conversion of ketone bodies to 14CO2 was slightly higher in fasted sheep (22%) compared to fed sheep (18%). Blood glucose and free fatty acid concentrations were decreased, but there was a significant increase in blood lactic acid and lactic acid production by the brain. The plasma insulin concentration was increased significantly both in fed and fasted animals. These results indicate that ovine brain can utilize ketone bodies irrespective of nutritional state. In addition, ketone bodies stimulated the production of lactate by ovine brain.
Blood flow to respiratory, cardiac, and limb muscles in dogs during graded exercise
Authors: Fixler DE , Atkins JM , Mitchell JH , Horwitz LD
Published: December 2017

The distribution of cardiac output was analyzed in six dogs, with the animals at rest and running on a level treadmill for 3 min at 3-4 mph (mild exercise) and 3 min at 6-8 mph (moderate exercise). Organ flows were measured using 25-mug-diam radioactive microspheres. Cardiac output averaged 2.5, 4.6, and 5.7 liters/min, for rest, mild exercise, and moderate exercise, respectively. The greatest change was in diaphragmatic flow which increased by 275% with mild exercise and 500% with moderate exercise. Flow to intercostal muscles increased by 160 and 186%, to the exercising gastrocnemius muscle by 153 and 224%, and to cardiac muscle by 57 and 109% during mild and moderate exercise, respectively. Renal and cerebral flows did not change significantly. Significant decreases in flow occurred in the small and large intestines during moderate exercise. It is concluded that the increase in cardiac output during submaximal exercise was redistributed in a manner which limited flow to the brain, intestines, and kidneys and increased flow flow to the diaphragm, heart, and limb muscles.
Water content of rat adipose tissue and isolated adipocytes in relation to cell size
Authors: DiGirolamo M , Owens JL
Published: December 2017

Epididymal adipose tissue composition and adipocyte water content were studied in male rats during growth and development of spontaneous obesity. The data show that a highly significant positive correlation exists between fat-cell volume and intracellular water space (IWS) (r=.967, P less than .001). Intracellular water, expressed as picoliters per fat cell, varied from 1.5-2 in small fat cells (mean vol, 30-50 pl) to 9-10 in large cells (800-1,000 pl). When expressed as percent of fat-cell volume, IWS varied from 5-7% in the small fat cells to 1-1.3% in the large ones. Total adipose tissue water continued to increase with increasing adipose mass. Similarly, total adipocyte water increased with enlarging cell size and tissue mass. The contribution of total adipocyte water (as contrasted to that of nonadipocyte water) to total tissue water, however, was found to be limited (less than 23%) and to decline progressively with adipose mass expansion.
Midbrain neuronal responses to local and spinal cord temperatures
Authors: Hori T , Harada Y
Published: December 2017

Water-perfused thermodes were implanted over the lumbothoracic spinal cord and unilaterally in the midbrain of urethan-anesthetized rabbits. Single-unit activities were recorded with steel microelectrodes from the thermosensitive neurons in the midbrain reticular formation (MRF), and the effects of heating and cooling of the spinal cord were studied. Of 38 cold-sensitive MRF neurons studied, 7 units decreased their firing rate upon elevation of spinal cord temperature (Tsc) and 3 units showed the opposite type of response to Tsc. The remaining 28 cold units were not affected by the changes in Tsc between 30 and 43 degrees C. Of 17 warm units, 3 units increased and one unit decreased the firing rate during spinal cord heating. These results suggest that the temperature signal arising from thermosensitive structures in the spinal cord may be transmitted to some of the locally thermosensitive neurons in the MRF.