bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemodynamics, fluid volume, and hormonal responses to chronic high-salt intake in dogs
Authors: Krieger J. E. , Liard J. F. , Cowley A. W.
Published: December 2017

The sequential hemodynamics, fluid and electrolyte balances, and the hormonal responses to a 7-day high-salt (NaCl) intake were investigated in sodium-depleted conscious dogs (n = 6). Studies were carried out in metabolic cages mounted on sensitive load cells, which enabled continuous 24 h/day monitoring of total body weight (TBW) as an index of changes in body water. Beat-by-beat hemodynamics were determined 24 h/day. Water (700 ml/day iv) intake was maintained constant. Daily fluid and electrolyte balances and hormonal analyses were performed. An increase of daily salt intake from 8 to 120 meq increased TBW 251 +/- 44 g (P less than 0.05), which was sustained thereafter. Average 24-h mean arterial pressure (MAP) and heart rate (HR) remained unchanged. Average cardiac output (CO) increased 11% (P less than 0.05) above control values by day 2, while total peripheral resistance (TPR) decreased proportionally. CO and TPR returned to control values only when low salt was resumed. Blood volume (BV) was unchanged on day 2 as indicated by direct measurement of BV (51Cr-labeled red blood cells) or by analysis of plasma protein concentration. A 92-meq (P less than 0.05) sodium retention was observed initially, and plasma sodium concentration increased slightly. Plasma renin activity, angiotensin II, and aldosterone levels decreased significantly, whereas vasopressin and atrial natriuretic peptide levels remained unchanged. In summary, chronic high-salt intake resulted in a net retention of water and sodium with no changes in MAP, HR, or BV. The rise in CO was offset by a reduction in TPR, which appeared at least in part related to angiotensin II suppression.
Late-onset renal hypertension in old rats alters myocardial microvessels
Authors: Tomanek R. J. , Aydelotte M. R. , Butters C. A.
Published: December 2017

We tested the hypothesis that late-onset hypertension in middle-aged (15 mo) and senescent (24 mo) rats would adversely affect the coronary microvasculature. Morphometric analyses were performed on coronary capillaries and arterioles from rats with one-kidney, figure-8 renal wrap hypertension of 3-mo duration. Compared with control rats, wall-to-lumen ratios of arterioles with lumen diameters less than 25 microns were higher in the two hypertensive groups by approximately 30%; larger arterioles did not show consistent intergroup differences. A comparison of the two control groups revealed that wall-to-lumen ratio of arterioles with lumen diameters less than 50 microns tended to be greater in the senescent rats. Capillary numerical density was markedly reduced in the hypertensive animals of both age groups and caused an increase in the mean Krough cylinder radius and in the mean capillary domain. The latter increased by 28-63%; the largest increment occurred in the endomyocardium of the senescent group. A trend toward increased heterogeneity of capillary spacing was also noted in the hypertensive rats. The observed microvascular alterations occurred in the absence of an absolute increase in left ventricular mass but in the presence of cardiocyte hypertrophy. Thus the decrements in capillary numerical density are not only due to inadequate growth but reflect an absolute reduction in the number of these vessels associated with cardiocyte loss. It is concluded that late-onset hypertension in middle-aged and senescent rats is characterized by left ventricular wall remodeling that includes microvascular alterations that would be expected to limit maximal myocardial flow and O2 supply to the cardiocyte.
Role of adenosine in regulation of regional cerebral blood flow in sensory cortex
Authors: Ko K. R. , Ngai A. C. , Winn H. R.
Published: December 2017

We have previously demonstrated that rat pial arterioles located on the somatosensory cortex dilated in response to contralateral sciatic nerve stimulation (SNS). We hypothesized that the vasodilation was mediated by adenosine, released as a result of somatosensory cortex activation. To test this hypothesis, we examined the effects of SNS (0.15-0.2 V, 5 ms, 5 Hz for 20 s) on pial arterioles under conditions of altered adenosine availability. Cerebrospinal fluid (CSF) adenosine was altered by perfusing mock CSF, under a cranial window in anesthetized rats, containing either an adenosine uptake competitor (dipyridamole or inosine) or an adenosine receptor blocker (theophylline). With CSF only, SNS caused pial arterioles (resting diam, 29 +/- 1 micron) to dilate by 38 +/- 10% (peak magnitude) for 32 +/- 2 s. Dipyridamole (10(-6) M) significantly (P less than 0.02) enhanced both the magnitude (to 62 +/- 12%) and duration (to 68 +/- 10 s) of the response. Similarly, inosine (10(-3) M) significantly (P less than 0.02) potentiated the vasodilative response from resting values of 27 +/- 5% and 34.8 +/- 4.1 s to 37 +/- 6% and 89.6 +/- 14.1 s. In contrast, theophylline (5 x 10(-5) M) significantly (P less than 0.001) attenuated arteriolar vasodilation from resting values of 38 +/- 5% and 29.3 +/- 1.2 s to 18 +/- 3% and 22.0 +/- 0.9 s. Neither dipyridamole nor theophylline had a significant effect on neuronal response (sensory-evoked response) recorded from the somatosensory cortex. These results suggest that adenosine is involved in the regulation of pial vasodilation during cerebral cortical activation.
ATP depletion and mitochondrial functional loss during ischemia in slow and fast heart-rate hearts
Authors: Rouslin W. , Broge C. W. , Grupp I. L.
Published: December 2017

In the present study, isolated dog and rat hearts were perfused in the Langendorff mode with Krebs bicarbonate buffer in the absence and presence of 10(-5) M oligomycin. The perfusion protocols employed allowed tissue pH to drop during subsequent ischemic incubations essentially as it would in blood-perfused hearts. Tissue pH, ATP, lactate, and mitochondrial respiratory function were measured during the course of subsequent zero-flow ischemic incubations. The adenosinetriphosphatase (ATPase) activities attributable to both mitochondrial and nonmitochondrial ATPases in sonicated heart homogenates and the actomyosin ATPase in isolated cardiac myofibrils were measured in both species. Consistent with earlier results with a different model in which tissue pH was buffered during the ischemic incubations [W. Rouslin, J. L. Erickson, and R. J. Solaro. Am. J. Physiol. 250 (Heart Circ. Physiol. 19): H503-H508, 1986], the inhibition of the mitochondrial ATPase in situ by oligomycin markedly slowed both tissue ATP depletion and the loss of mitochondrial function during ischemia in the dog. However, oligomycin had only a very small and transient effect on ATP depletion and mitochondrial function in the rat. This was apparently so because of the fivefold higher rate of glycolytic ATP production as well as the nearly threefold higher total nonmitochondrial ATPase activity of ischemic rat compared with ischemic dog heart. These results suggest that although the inhibition of the mitochondrial ATPase makes a major contribution to ATP conservation in ischemic dog heart, it makes only a very small contribution in rat.
Skin vascular bed is a potential blood reservoir during heat stress
Authors: Deschamps A. , Magder S.
Published: December 2017

To determine the potential role of the skin vasculature as a blood reservoir, we measured venous compliance (Cv), resistance (Rv), and their product, the time constant of venous drainage (tau sk = RvCv), in skin flaps from the hindlimbs of 15 dogs anesthetized with pentobarbital sodium at different core temperatures (Tc, 37-42 degrees C), skin temperature (Ts, 25.3-50.0 degrees C), and during an infusion of papaverine (5%). The vasculature of the flap was isolated, and a double-occlusion technique was used to measure the static pressure in the venous compartment. The blood volume of the flap was altered by changing either flow or outflow pressure (Pv). The change in volume was estimated from the change in weight of the flap with a force transducer. At Tc = 37 degrees C, Rv was 2.27 +/- 0.81 mmHg.min.ml-1.100 g-1 (means +/- SD), Cv was 0.17 +/- 0.06 ml.mmHg-1.100 g-1, and tau sk was 28.0 +/- 8.8 s. Rv decreased with elevated Tc, Ts, and with papaverine. Cv increased with a rise in Tc and Ts. Increasing Tc and Ts did not change tau sk, but the papaverine infusion shortened it. The lowest tau sk (20 s) occurred during maximal vasodilatation. This long tau sk indicates that the skin could serve as a blood reservoir during heat stress.
Effects of skeletal muscle fiber deformation on lymphatic volumes
Authors: Mazzoni M. C. , Skalak T. C. , Schmid-Schonbein G. W.
Published: December 2017

Because lymphatics in skeletal muscle have no smooth muscle, they are expanded and compressed solely by stresses in the surrounding tissue. Whole organ experiments have indicated that lymph flow is significantly elevated during muscle activity, yet the underlying mechanism for lymph formation has not been identified. To investigate this mechanism, specimens of the rat spinotrapezius muscle were fixed in situ at the undeformed in vivo length, and also in the stretched and contracted states, for histological examination. Cross-sectional areas of lymphatic vessels, skeletal muscle fibers, blood vessels, and interstitial space were measured using a stereological technique. The in situ preparation with intact muscle fascia was essential for preservation of interstitial volume. The lymphatic cross-sectional areas and muscle stretch ratios from 20 rats showed that lymphatic volume increased by 57% for a 20% stretch, and decreased by 45% for a 20% contraction. Deformation of the incompressible muscle fibers appears to inversely affect surrounding tissue structures; e.g., decreased fiber cross-sectional area during stretch increases interstitial spacing between fibers, which in turn expands lymphatics.
New technique to completely isolate carotid sinus baroreceptor regions in rats
Authors: Shoukas A. A. , Callahan C. A. , Lash J. M. , Haase E. B.
Published: December 2017

We developed a method by which we can completely isolate the carotid sinus baroreceptor regions in the rat. The carotid sinus baroreceptor region is exposed and, with the use of extra-fine forceps, a human hair is placed around and tied at the root of the bifurcation. This procedure occludes the external carotid artery and blood flow to the carotid body. An injector is then attached to a catheter in the common carotid artery. We introduce a cylindrical rubber plug into either the palentine or internal carotid artery. A second plug is introduced to occlude the other artery. In six of the eight rats studied, these procedures completely isolated the carotid sinus region. In those cases where a small leak persisted at a carotid sinus pressure of 180 mmHg, we introduced a small particle of the animal's own previously clotted blood. Carotid sinus pressure was either randomly changed between 40 and 180 mmHg in 20-mmHg increments or in sequential 20-mmHg steps from 40 to 180 mmHg while measuring the animal's pulsatile and mean blood pressures. Arterial pressure-carotid sinus pressure relationship indicates that there is a highly sigmoidal relationship between the two pressures. The peak gain of the carotid sinus reflex system had a range from 1.5 to 4.0 and a mean value of 2.07 +/- 0.08. Our data indicate that the rat exhibits a significant carotid sinus baroreceptor reflex response. This technique combined with other techniques will allow for the study of neural control of cardiovascular function in the rat.
Sexual dimorphism in vasopressin-induced contraction of rat aorta
Authors: Stallone J. N. , Crofton J. T. , Share L.
Published: December 2017

Previously, we reported that, in the rat, pressor responsiveness to vasopressin (VP) is higher in males than in females during most phases of the estrous cycle. To explore the role of the vasculature in this phenomenon, we examined vascular reactivity to VP in thoracic aortas of male rats and female rats during each phase of the estrous cycle. Aortic rings were prepared from age-matched male and female Sprague-Dawley rats and mounted for isometric tension recording. Maximal response of female aortas to VP (4,246 +/- 163 mg/mg ring dry wt) was more than twice (P less than 0.001) that of male aortas (1,877 +/- 215 mg/mg ring wt). Sensitivity of female aortas to VP was substantially higher (P less than 0.001) than that of male aortas (EC50: 10.9 +/- 0.7 vs. 19.0 +/- 1.6 nM, respectively). Maximal rate of tension development (dT/dtmax) during contraction with VP was nearly twofold higher (P less than 0.01) in female aortas (536 +/- 23 mg/min) than in male aortas (300 +/- 19 mg/min). Maximal response, sensitivity, and dT/dtmax of female aortas did not vary significantly during the estrous cycle. Maximal response of female aortas to phenylephrine (PE; 1,251 +/- 93 mg/mg ring wt) was half that (P less than 0.001) of male aortas (2,546 +/- 194 mg/mg ring wt); sensitivity to PE did not differ significantly (EC50: 0.33 +/- 0.02 vs. 0.38 +/- 0.06 microM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Alpha 1-adrenergic blockade does not alter control of skin blood flow during exercise
Authors: Kenney W. L. , Tankersley C. G. , Newswanger D. L. , Puhl S. M.
Published: December 2017

Human skin blood flow (SkBF) is controlled by both an alpha-adrenergic vasoconstrictor system and an active vasodilator system. During upright dynamic exercise, SkBF increases linearly with increasing body core temperature (Tc) until higher (i.e., greater than 38 degrees C) Tcs, beyond which little further increase in SkBF occurs. To examine the role of the two efferent control arms in this attenuated SkBF rise, we tested nine men (aged 25-53 yr) with and without (placebo) orally administered prazosin HCl (an alpha 1-adrenergic antagonist) during 1 h of moderate cycle exercise (100 W) in a warm (36 degrees C, 45% relative humidity) environment. Blockade of reflex vasoconstriction was verified via a cold challenge. During exercise, mean arterial pressure (MAP, brachial auscultation) was significantly lower (P less than 0.03) and heart rate significantly higher (P less than 0.02) during the prazosin trials; plasma catecholamine concentrations were unaffected. Neither esophageal temperature (Tes) nor mean skin temperature was affected by the drug during exercise. Forearm vascular conductance (FVC) was calculated from forearm blood flow (FBF, venous occlusion plethysmography) and MAP (FVC = FBF/MAP). FVC plotted as a function of time or Tes resulted in coincident response patterns for the placebo and prazosin treatments, reaching a plateau at a Tes of about 38 degrees C. The responses of the older men were not selectively altered by prazosin treatment, indicating that the lower FBF responses previously seen in older subjects during exercise in the heat does not appear to be the result of an increased alpha 1-adrenergic tone.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanisms of rate staircase in rat ventricular cells
Authors: Borzak S. , Murphy S. , Marsh J. D.
Published: December 2017

We studied the steady-state rate staircase in isolated rat ventricular cells stimulated at frequencies ranging up to 6 Hz at 37 degrees C. When contractility was measured as displacement of the cell edge, amplitude of motion decreased while stimulation rates were increased from rest to 1 Hz (negative staircase). With further increases in the rate of stimulation to 6 Hz, amplitude of motion increased for each increment in stimulation rate (positive staircase). Ryanodine at a concentration of 100 nM was a negative inotrope and abolished the rested state contraction and the negative staircase seen between rest and 1 Hz (P less than 0.05) but had no significant effect on twitch amplitude or the staircase at stimulation rates between 1 and 6 Hz. L-type Ca2+ channel inhibition with verapamil (0.2 microM) had little effect on twitch or the negative staircase from rest to 1 Hz, but twitch amplitude was diminished and the staircase was converted from positive to negative at stimulation rates between 1 and 6 Hz (P less than 0.05). We conclude that in rat ventricular cells studied at 37 degrees C, the rate staircase is biphasic: negative from rest to 1 Hz and positive from 1 to 6 Hz. This phenomenon is dominated by Ca2+ release from the sarcoplasmic reticulum at rates less than 1 Hz and by Ca2+ entry through L channels at rates greater than 1 Hz.
Influence of low perfusion pressure on effect of endothelin on coronary vascular bed
Authors: Clozel J. P. , Sprecher U.
Published: December 2017

The goal of this study was to evaluate the influence of low coronary perfusion pressure on the coronary vasoconstriction induced by endothelin. For this purpose, the circumflex coronary arteries of 12 open-chest dogs were cannulated and perfused at a controlled pressure. Total coronary blood flow was measured with an electromagnetic flowmeter and the transmural distribution of coronary blood flow with the radioactive microspheres technique. In addition, the circumflex coronary artery diameter was measured by sonomicrometry with piezoelectric crystals, and the coronary cross-sectional area was calculated. At a coronary perfusion pressure of 100 mmHg, endothelin induced a marked coronary vasoconstriction and a redistribution of coronary blood flow toward the endocardium. At a low coronary perfusion pressure of 40 mmHg, these effects of endothelin were still present. The constriction of the large coronary artery occurred even with a lower dose of endothelin at a low coronary perfusion pressure compared with the normal perfusion pressure. This was not the case when angiotensin II was given the same way. We conclude that endothelin is a potent coronary vasoconstrictor even at a low perfusion pressure. Thus one may speculate that endothelin plays a role in the coronary spasm which has been shown in patients with angina pectoris.
Alpha 1-adrenergic stimulation is coupled to cardiac myocyte hypertrophy
Authors: Ikeda U. , Tsuruya Y. , Yaginuma T.
Published: December 2017

We have investigated whether alpha 1-adrenergic stimulation is coupled to myocardial hypertrophy in adult rat ventricular cells (ARVC) in culture. Exposure of ARVC to norepinephrine (NE) caused a significant increase in [3H]-leucine incorporation and total protein content in ARVC. Prazosin totally inhibited the NE-stimulated leucine uptake by ARVC. Inhibition of spontaneous contraction of ARVC with KCl or verapamil did not prevent the stimulation of hypertrophy by NE. Protooncogene c-myc expression in ARVC was induced at 1 h after exposure to NE. Above results support the premise that activation of the alpha 1-adrenergic receptors by NE induces hypertrophy of ARVC, independent of changes in contractile activity.
Differential control of renal and splenic nerves without medullary topography
Authors: Beluli D. J. , Weaver L. C.
Published: December 2017

A previous study in our laboratory showed that pharmacological blockade of neurons in the rostral ventrolateral medulla has greater influence on the electrical activity of renal than splenic nerves (K. Hayes and L. C. Weaver, J. Physiol. Lond. 428: 371-385, 1990). This differential control of sympathetic nerves innervating different organs may be due to viscerotopic representation of the kidney and spleen within medullary neurons that control the vasculature. To search for this topographical organization, 15 nl (2.5 nmol) of the excitatory amino acid DL-homocysteic acid (DLH) was microinjected into the ventrolateral medulla (VLM) of rats anesthetized with urethan. No distinct viscerotopic organization was found in the rostral or caudal VLM. However, renal nerve responses were consistently greater than splenic by a fixed proportion. In summary, stimulation of rostral and caudal VLM neurons causes differential renal and splenic excitatory responses, but mechanisms providing this selective control do not involve spatial organization of neuronal groups in the VLM.
Sensitization of baroreceptor reflex by central endothelin in conscious rats
Authors: Itoh S. , van den Buuse M.
Published: December 2017

Effect of centrally administered endothelins (ETs) on cardiovascular regulation was investigated in conscious normotensive rats. ET-1, ET-2, or ET-3 was injected through a cannula into the cisterna magna, and mean arterial pressure (MAP) and heart rate (HR) were measured through a cannula in the femoral artery. Baroreceptor HR reflex was measured by monitoring the changes in HR in response to changes in MAP induced by slow intravenous injection of phenylephrine or nitroprusside. MAP and HR responses were then analyzed in individual animals by sigmoidal curve fitting. Intracisternal (ic) administration of ET-1 did not change resting MAP or HR at doses of 2.5 or 25 pmol/kg. The higher dose of ET-1 induced a significant increase of baroreflex sensitivity without a change of HR range. Sympathetic and vagal components of the baroreflex were examined by testing reflex responses after pretreatment with methylatropine (0.5 mg/kg iv) and atenolol (1.0 mg/kg iv), respectively. An increased baroreflex sensitivity was observed after ET-1 treatment in the atenolol-treated rats but not in the methylatropine-treated rats, suggesting that the peptide selectively affected the vagal component of the reflex. Intravenous 25 pmol/kg ET-1 did not cause an increase in baroreflex sensitivity. Neither ET-2 nor ET-3 (25 pmol/kg ic) induced changes in resting MAP or HR, but both significantly increased baroreflex sensitivity without changes in HR range. Order of potency of the ETs on baroreflex gain was ET-3 greater than or equal to ET-1 greater than ET-2. In conclusion, ETs at doses that do not change resting values for MAP or HR, may induce significant centrally mediated sensitization of the baroreceptor HR reflex.(ABSTRACT TRUNCATED AT 250 WORDS)
Cooling augments alpha 2-adrenoceptor-mediated contractions in rat tail artery
Authors: Harker C. T. , Ousley P. J. , Bowman C. J. , Porter J. M.
Published: December 2017

Experiments were performed to assess the effects of acute moderate cooling on postjunctional alpha 1- and alpha 2-adrenoceptors in isolated rings of tail arteries from male Sprague-Dawley rats. Rings were contracted with norepinephrine (NE; 10(-9) to 10(-4) M) alone or in the presence of prazosin (Pz; 3 x 10(-7) M) or rauwolscine (Rw; 10(-7) M). NE concentration-response curves were inhibited by alpha 1-blockade (Pz) but not significantly affected by alpha 2-blockade (Rw). In all rings, cooling caused an increase in the slope of the dose-response curve and a significant increase in the concentration of agonist required to evoke contractions, as assessed by that concentration of NE required to evoke a contraction equal to 10% of maximal (EC10). Cooling inhibited contractions evoked by the selective alpha 1-adrenergic agonist phenylephrine (PE) as assessed by EC10 but had no significant effect on the weak contractions elicited by the selective alpha 2-adrenergic agonist B-HT 920. Prior elevation of tone with either KCl or prostaglandin F2 alpha enhanced alpha 2-mediated contractions. These contractions were augmented by cooling, whereas those caused by either KCl or prostaglandin F2 alpha alone were not significantly affected. Our results suggest that alpha 2-adrenoceptor-mediated responses in this blood vessel are dependent on the level of preexisting tone and are potentiated by cooling.
Umbilical and hepatic venous responses to circulating vasoconstrictive hormones in fetal lamb
Authors: Paulick R. P. , Meyers R. L. , Rudolph C. D. , Rudolph A. M.
Published: December 2017

Acute fetal hypoxemia increases the vascular resistance of the umbilical veins as well as that of the liver. Because, at least in the human, the umbilical-placental circulation has no autonomic innervation, circulating hormones could well be responsible for this increase in umbilical-placental outflow resistance. In chronically instrumented fetal sheep, norepinephrine, epinephrine, vasopressin, and angiotensin II were infused in sequentially increasing doses into the descending aorta and vascular resistance to umbilical-placental blood flow was measured. Norepinephrine and epinephrine increased the vascular resistance of the umbilical veins in a dose-dependent manner. Both catecholamines also increased the vascular resistance of the liver, resulting in an increase in ductus venosus blood flow. In contrast, vasopressin and angiotensin II had no effect on umbilical-placental outflow resistance. Thus catecholamines may be responsible for the increase in the vascular resistance of the umbilical veins and liver in response to acute fetal hypoxemia.
Norepinephrine kinetics and cardiac output during nonhypotensive lower body negative pressure
Authors: Baily R. G. , Leuenberger U. , Leaman G. , Silber D. , Sinoway L. I.
Published: December 2017

Recently we have shown that arterial norepinephrine (NE) concentration increases significantly during lower body negative pressure (LBNP) of -15 mmHg. Interestingly, the increase was found to be related predominantly to a decrease in arterial NE clearance. We postulated that this reduction in clearance would be related to a reduction in cardiac output. Accordingly, we measured both cardiac output (2-dimensional echocardiographic/Doppler technique) and arterial NE kinetics ([3H]NE continuous infusion radiotracer technique) during LBNP of -15 mmHg. These measures of cardiac output and arterial NE spillover and clearance were obtained in 12 normal subjects at baseline, 5 and 10 min (Early) and 25 and 30 min (Late) of LBNP. We found that arterial NE concentration increased significantly, by 25% Early and 22% Late (P = 0.001). Spillover, however, did not change (P = 0.258), whereas clearance decreased by 12% Early and 19% Late (P = 0.014), and cardiac output decreased by 15% Early and 19% Late (P = 0.001). These reductions in clearance and cardiac output correlated significantly (r = 0.61, P = 0.001). No correlation was noted between spillover and cardiac output (r = 0.027, P = 0.874). We conclude that the increases in arterial NE concentration during nonhypotensive LBNP are predominantly due to decreased cardiac output with resultant decreases in systemic clearance of NE. These findings suggest that the ability to clear NE from the circulation is linked to the level of cardiac output and that low cardiac output states by themselves may lead to an elevation in arterial plasma NE concentrations.
Assessment of elastin and collagen contribution to aortic elasticity in conscious dogs
Authors: Armentano R. L. , Levenson J. , Barra J. G. , Fischer E. I. , Breitbart G. J. , Pichel R. H. , Simon A.
Published: December 2017

The elastic behavior of total elastin (EE) and collagen (EC) and the recruitment of collagen fibers (FC) supporting wall stress at a given transmural pressure level were assessed in seven conscious dogs using descending thoracic aortic pressure (microtransducer) and diameter (sonomicrometer) measurements. Stress-strain relationships values calculated at control and during bolus administration of angiotensin and nitroglycerin enabled quantification of angiotensin and nitroglycerin enabled quantification of elastic moduli of elastin (EE = 4.868 +/- 1.753 x 10(6) dyn/cm2; means +/- SD) and collagen (EC = 1,306 +/- 637 x 10(6) dyn/cm2) according to a biphasic model of elastin and collagen parallel arrangement. The FC was found to be 6.1 +/- 2.6% at a pressure level of 118 +/- 16 mmHg. Values for EE and EC were similar to those reported in in vitro studies and showed scarce variability. This approach provides a quantitative evaluation of elastin and collagen moduli in conscious animals and also permits the evaluation of FC, which may be of interest in studies of connective tissue diseases involving the aortic wall.
Effect of chronic verapamil treatment on ventricular function and growth in chick embryos
Authors: Clark E. B. , Hu N. , Turner D. R. , Litter J. E. , Hansen J.
Published: December 2017

Adjustment of myocardial mass to work load is a fundamental characteristic of the heart. We studied the effect of verapamil, a calcium channel blocker, on growth and function of chick embryonic ventricle. We treated stage 18 chick embryos with verapamil delivered to the extraembryonic vascular bed by a miniosmotic pump and compared them with saline-treated control and untreated embryos. At stages 24, 27, and 29, we measured ventricular pressure and dP/dt by a servo-null system, dorsal aortic stroke volume and dV/dt by pulsed-Doppler, and ventricular and embryo wet weights. Mean myocyte profile area was measured by digital planimetry technique, and cell growth response by DNA and protein assay. Verapamil treatment decreased ventricular pressure in experimental (P less than 0.05) compared with saline control and normal embryos; at stage 27, 1.59 +/- 0.21 vs. 2.17 +/- 0.05 and 2.35 +/- 0.08 (SE) mmHg, respectively. Mean dorsal aortic blood flow decreased in experimental (P less than 0.05) vs. control and normal embryos; at stage 27, 0.98 +/- 0.07 vs. 1.54 +/- 0.10 and 1.56 +/- 0.07 mm3/s, respectively. Stroke volume remained the same in all experimental, normal, and control embryos except at stage 29. Ventricular weight decreased in experimental (P less than 0.05) vs. control and normal embryos; at stage 27, 1.09 +/- 0.07 vs. 1.51 +/- 0.08 and 1.54 +/- 0.11 mg, respectively. Embryo weights, myocyte size, and cytoplasmic fractional volume were similar in all groups. Morphology of ventricles was normal. DNA was lower in experimental (P less than 0.05) compared with control and normal embryos.(ABSTRACT TRUNCATED AT 250 WORDS)
Pressure-independent arteriolar rarefaction in hypertension
Authors: Boegehold M. A. , Johnson M. D. , Overbeck H. W.
Published: December 2017

To assess the role of pressure in the arteriolar rarefaction associated with hypertension, we studied microvascular density in a hindquarters muscle (cremaster) of rats, 8 wk after coarctation (n = 8) or sham-coarctation (n = 10) of the abdominal aorta. To document the level of arterial pressure in hindquarters vascular beds of similar rats 8-9 wk after initial surgery, we implanted femoral arterial catheters under anesthesia and, 2-5 days later, we measured conscious femoral arterial pressures in coarcted [93 +/- 4 (SE) mmHg; n = 7] and sham-coarcted (110 +/- 3 mmHg; n = 4) rats. The cremaster muscle microcirculation was examined after fixation and Microfil infusion at in vivo pressures. The density of distal third- to fourth-order arterioles was lower by 19% (P = 0.03) in coarcted (1.37 +/- 0.06 mm/mm2) than in sham-coarcted (1.69 +/- 0.11 mm/mm2) rats. We conclude that pressure-independent mechanisms are involved in the arteriolar rarefaction accompanying hypertension.
Vascular responses of umbilical-placental circulation to vasodilators in fetal lambs
Authors: Paulick R. P. , Meyers R. L. , Rudolph A. M.
Published: December 2017

It has been suggested that the umbilical-placental circulation is maximally vasodilated under normal conditions. To test this hypothesis, we investigated the effect of vasodilators on umbilical-placental vascular resistance. In nine chronically instrumented fetal lambs, catheters were placed in the descending aorta, umbilical artery, umbilical vein, and inferior vena cava. Umbilical-placental blood flow was measured by an electromagnetic flow probe placed around the common umbilical artery. Forskolin and nitroglycerin both dilated the umbilical-placental circulation, causing a dose-dependent decrease in umbilical-placental resistance to approximately 80% of baseline, indicating that the umbilical-placental circulation has some dilatory reserve. Both the adenosine 3',5'-cyclic monophosphate and the guanosine 3',5'-cyclic monophosphate mechanisms, which are directly stimulated by forskolin and nitroglycerin, respectively, are functional in the umbilical-placental circulation. However, the vasodilators prostacyclin and adenosine, which act through specific cell membrane receptors, have no effect on the umbilical-placental resistance. The inability of these agents to dilate the umbilical-placental circulation could be due to a lack of the appropriate receptors in the umbilical-placental vasculature.
Collagen remodeling and changes in LV function during development and recovery from supraventricular tachycardia
Authors: Spinale F. G. , Tomita M. , Zellner J. L. , Cook J. C. , Crawford F. A. , Zile M. R.
Published: December 2017

Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dYsfunction and dilatation. Termination of SVT appears to improve symptoms of congestive heart failure. However, the structural events that occur during development and regression of SVT-induced cardiomyopathy are unknown. Accordingly, LV function (simultaneous echocardiogram-catheterization) and collagen content and distribution were measured in pigs (23-25 kg) assigned to three groups: 1) rapid atrial pacing (240 beats/min) for 3 wk (SVT, n = 10); 2) SVT for 3 wk, followed by deactivation of the pacemaker and a 4-wk recovery period (PST, n = 9); and 3) sham-operated controls (CON, n = 10). LV fractional shortening was 30 +/- 2% in CON, fell to 13 +/- 2% with SVT (P less than 0.05), and returned to CON values with PST (31 +/- 2%). SVT resulted in significantly increased LV end-diastolic dimension compared with CON (4.9 +/- 0.3 vs. 3.5 +/- 0.2 cm, P less than 0.05) and no change in LV wt/body wt (2.7 +/- 0.2 vs. 2.6 +/- 0.2 g/kg, P = 0.85). Termination of SVT (PST) resulted in development of hypertrophy, LV mass increased to 3.50 +/- 0.3 g/kg (P less than 0.05 vs. CON). With the use of pressure-dimension-thickness relations during diastole, the regional chamber stiffness constant (Kc) was computed. Kc was unchanged by SVT compared with CON (5.3 +/- 1.4 vs. 3.7 +/- 0.5, P greater than 0.35) but increased with PST (7.4 +/- 0.6, P less than 0.05). LV hydroxyproline content significantly fell with SVT compared with CON (2.24 +/- 0.58 vs. 2.68 +/- 0.45 mg/g dry wt, P less than 0.05, respectively) and significantly increased with PST (3.68 +/- 0.85 mg/g dry wt, P less than 0.05). With the use of transmission electron microscopy, collagen fibril diameter was reduced with SVT compared with CON (1.45 +/- 0.5 vs. 1.7 +/- 0.5 microns, P less than 0.05) and increased with PST (3.3 +/- 1.4 microns, P less than 0.05). Scanning electron microscopy revealed disruption of collagen struts between adjacent SVT myocytes and a thickened collagen weave with PST. Thus chronic SVT resulted in systolic and diastolic dysfunction and reduced collagen support of adjoining myocytes. Early recovery from SVT was associated with LV hypertrophy, increased collagen, and increased LV stiffness.
Adenosine receptor-mediated coronary artery relaxation and cyclic nucleotide production
Authors: Cushing D. J. , Brown G. L. , Sabouni M. H. , Mustafa S. J.
Published: December 2017

We investigated the involvement of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) in adenosine (ADO) receptor-mediated coronary artery relaxation. Rings from left anterior descending coronary artery, with the endothelium mechanically removed, contracted with prostaglandin F2 alpha and relaxed in a concentration-dependent manner to ADO, 2-chloroadenosine (CAD), l-N6-(2-phenylisopropyl)adenosine (R-PIA), and 5'-(N-ethylcarboxamido)adenosine (NECA). These relaxations were blocked by addition of the ADO receptor antagonist 8-(sulfophenyl)theophylline (8-SPT), indicating ADO receptor involvement. In an endothelium-free membrane preparation, ADO, CAD, and R-PIA all stimulated adenylate cyclase activity in a concentration-dependent manner, and these responses were blocked by 8-SPT. The increase in adenylate cyclase activity produced by ADO, CAD, and R-PIA was completely dependent on the presence of guanosine 5'-triphosphate, suggesting G protein involvement. Surprisingly, NECA and CGS-21680 did not increase adenylate cyclase activity. Unlike atrial natriuretic factor, neither NECA, CAD, R-PIA, nor ADO increased guanylate cyclase activity, suggesting that cGMP is not involved in ADO receptor-mediated relaxation. Data presented in this study support the hypothesis that ADO receptor-mediated coronary artery relaxation may involve cAMP; however, the inability of NECA and CGS-21680 to stimulate adenylate cyclase suggests that the ADO receptor-signaling mechanisms in coronary artery may be more complicated than agonist interaction with a single adenylate cyclase-coupled A2 adenosine receptor.
Vasorelaxant effects of short chain fatty acid salts in rat caudal artery
Authors: Nutting C. W. , Islam S. , Daugirdas J. T.
Published: December 2017

Acetate relaxes rat caudal artery and increases tissue adenosine 3',5'-cyclic monophosphate (cAMP) levels. The present study's purpose was to determine whether related ultrashort chain (volatile) fatty acids, propionate (C3), butyrate (C4), and octanoate (C8) would do so as well. It was found that butyrate and propionate had very similar vasorelaxant profiles to acetate; they relaxed caudal artery strips precontracted with KCl, phenylephrine, arginine vasopressin, and prostaglandin F2 alpha. The vasorelaxation was endothelium independent, was not blocked by indomethacin, and was associated with a rise in tissue cAMP levels but not in guanosine 3',5'-cyclic monophosphate (cGMP) levels. The mean effective concentration for butyrate (0.8 mM) was lower than that for acetate (2.0 mM) or propionate (1.9 mM). Propionate-mediated relaxation was blocked by the stilbene inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Vasorelaxant effects of octanoate were also not dependent on endothelium and were not affected by indomethacin. Maximal vasorelaxant effect of octanoate was greater than that of acetate, propionate, or butyrate; vasorelaxant effect of octanoate was only slightly attenuated by DIDS and was associated with only a minimal effect on tissue cAMP levels. Results suggest that vasodilatory effects of acetate generalize to propionate and butyrate, but that vasorelaxant effects of octanoate may be occurring via a separate mechanism.
Load-dependent left ventricular relaxation in conscious dogs
Authors: Zile M. R. , Gaasch W. H.
Published: December 2017

Load-dependent relaxation was studied in eight conscious dogs by inflating an intra-aortic balloon during late systole. Initially, the balloon was inflated at the aortic dicrotic notch and deflated before the next systole; subsequently, the inflation time was moved progressively earlier in 30-ms steps. This intervention produced an abrupt increment in left ventricular (LV) systolic pressure. The contraction duration was assessed by measuring the time required for LV pressure to fall by 50% of its maximum value (P50). The rate of LV pressure decline was assessed by measuring its peak negative first time derivative (-dP/dt) and the time constant of relaxation (tau). When the balloon was inflated during late systole (50 +/- 5 ms before aortic dicrotic notch), the time to peak -dP/dt fell, P50 fell, peak -dP/dt increased, and tau was unchanged. Thus the initial rate of LV pressure decline was accelerated, and the duration of the contraction was abbreviated. These data indicated that myocardial relaxation in the intact conscious dog is load dependent. Late systolic balloon inflations were performed after treatment with propranolol, verapamil, or caffeine. During propranolol and verapamil, the rate of LV relaxation (peak -dP/dt and tau) was slowed; however, the effects of balloon inflation on LV pressure transients were qualitatively similar to that seen in the baseline state. By contrast, caffeine prevented the abbreviation in the contraction duration caused by late-systolic balloon inflation. Thus LV relaxation remained load dependent when myocardial relaxation was slowed by propranolol or verapamil; load-dependent relaxation was attenuated by caffeine, presumably due to its influence on the sarcoplasmic reticulum.
Cerebrovascular effects produced by electrical stimulation of fastigial nucleus
Authors: Talman W. T. , Dragon D. M. , Heistad D. D. , Ohta H.
Published: December 2017

We used the microsphere technique and laser flowmetry to assess cerebral blood flow in 43 anesthetized rats. Cerebral blood flow did not increase significantly when the fastigial nucleus was stimulated 15 min after administration of alpha-chloralose. In animals that received maintenance doses of alpha-chloralose, the modest (50%) increase in cerebral blood flow that did occur returned toward control during stimulation despite a continued stable elevation of arterial pressure. Stimulation of fastigial nucleus 2 h after alpha-chloralose elicited a 20 +/- 3 mmHg increase in arterial pressure; cerebral blood flow increased gradually for 30-60 s after the rise in arterial pressure and reached a peak that was approximately 90% (P less than 0.05) above baseline. The stimuli did not significantly reduce vascular resistance or impair autoregulation. We did not stimulate the fastigial nucleus for more than 2 h after administration of alpha-chloralose because anesthesia was effective for only 2 h. This study demonstrates that stimulation of the fastigial nucleus in rat produces a delayed increase in cerebral blood flow that is blocked by alpha-chloralose anesthesia. The delay in increases of cerebral blood flow suggests that a metabolic mechanism, not a direct neurogenic vascular effect, may account for increases in flow with fastigial stimulation.
Inhibition of brain glutamine accumulation prevents cerebral edema in hyperammonemic rats
Authors: Takahashi H. , Koehler R. C. , Brusilow S. W. , Traystman R. J.
Published: December 2017

The mechanism of brain swelling during hyperammonemia is not understood, but glutamine accumulation is consistently observed. We tested the hypothesis that brain swelling associated with hyperammonemia is a consequence of the osmotic effect of intracellular glutamine accumulation in brain. Increases in plasma ammonium levels from 31 +/- 3 to 601 +/- 38 mumol/l (+/- SE) were produced by 6 h of infusion of ammonium acetate in anesthetized rats. Hyperammonemia resulted in increased brain water content accompanied by more than a tripling of brain glutamine concentration compared with control rats receiving sodium acetate (5.6 +/- 0.4 vs. 18.8 +/- 0.4 mmol/kg). Inhibition of glutamine synthetase activity by pretreatment with L-methionine sulfoximine prevented both the increase in brain glutamine levels and the increase in brain water content despite elevated plasma ammonium levels (908 +/- 196 mumol/l). Thus cerebral edema during hyperammonemia is associated with glutamine accumulation. We suggest that accumulated glutamine may serve as an idiogenic osmole causing swelling. Because brain swelling eventually leads to increased intracranial pressure and tissue hypoxia, these data suggest a unifying mechanism to account for the many pathophysiological abnormalities found during coma associated with various forms of liver disease, inborn errors of metabolism, and Reye's syndrome.
Metabolic and functional consequences of blunted myocardial reactive hyperemia
Authors: Schwartz G. G. , Schaefer S. , Trocha S. D. , Steinman S. , Gober J. , Garcia J. , Massie B. , Weiner M. W.
Published: December 2017

This study determined whether the rapidity of myocardial metabolic and contractile recovery after brief coronary occlusion depends upon the intensity of reactive hyperemia. We also tested the hypothesis that coronary flow rate modulates contractility after brief myocardial ischemia, independent of changes in phosphorus metabolites. Eight open-chest pigs were studied with phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy with 14 s time resolution. After a 29-s anterior descending coronary occlusion, peak Doppler coronary flow velocity was alternately unrestricted (normal hyperemia, 443 +/- 40% of control) or limited to 159 +/- 9% of control. During 29 s coronary occlusion, phosphocreatine-to-inorganic phosphate ratio (PCr/Pi) and systolic segment shortening in the ischemic region fell to 28 +/- 4 and 7 +/- 7% of control, respectively. With normal hyperemia, PCr/Pi and segment shortening recovered within 29 s. With blunted hyperemia, recovery of both parameters was delayed an additional 29-43 s, associated with reduced subendocardial blood flow (measured with radioactive microspheres) and persistent intracellular acidosis. However, the relationship between segment shortening and PCr/Pi was unaffected by the intensity of reactive hyperemia. Thus blunted reactive hyperemia significantly delays metabolic and contractile recovery from brief ischemia, probably via transient maldistribution of transmural perfusion. However, coronary blood flow rate does not independently modulate contractility after brief reversible ischemia.
Endothelin: localization, synthesis, activity, and receptor types in human penile corpus cavernosum
Authors: Saenz de Tejada I. , Carson M. P. , de las Morenas A. , Goldstein I. , Traish A. M.
Published: December 2017

The localization, synthesis, and activity of endothelin and the receptor types mediating its effects in penile corpus cavernosum were investigated in whole tissue and in cultured cells derived from this tissue. With immunocytochemistry, utilizing an antiendothelin 1 (ET-1) monoclonal antibody, endothelin-like immunoreactivity was localized intensely in the endothelium and to a lesser degree in the trabecular smooth muscle. Human corpus cavernosum endothelial cells in culture expressed preproendothelin 1 mRNA, as determined by Northern blot analysis. Significant amounts of endothelin-like immunoreactivity were measured by radioimmunoassay in the supernatants of corpus cavernosum endothelial cells in culture. Endothelins are potent constrictors and caused long-lasting contractions of corporeal strips in organ chambers. Equilibrium binding analysis of endothelins to their receptor sites revealed high-affinity, specific, and saturable binding of labeled endothelins to corporeal membranes. Competition binding experiments demonstrated receptors with high affinity for ET-1 and -2 and low affinity for ET-3 and another, less abundant, set of receptors with high affinity for ET-1, -2, and -3. Affinity labeling of endothelins to corporeal membranes, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, revealed that ET-1 and -2 cross-linked specifically to three different molecular mass components (75, 52, and 34 kDa). ET-3 bound only to the 34-kDa component. It is concluded that human corpus cavernosum endothelium has the ability to synthesize and release endothelin, that endothelins contract corporeal smooth muscle, and that at least two distinct endothelin receptors may exist and are differentiated by their affinity for ET-3.
Albumin outflow into deep cervical lymph from different regions of rabbit brain
Authors: Yamada S. , DePasquale M. , Patlak C. S. , Cserr H. F.
Published: December 2017

Dynamics and pathways of 125I-labeled albumin (RISA) outflow from brain to deep cervical lymph have been studied in anesthetized rabbits between 4 and 25 h after microinjection of 1 microliter RISA into the internal capsule or midbrain. Lymph from the jugular lymph trunks was collected for periods of 2-11 h. RISA was cleared from brain with half-times of disappearance from internal capsule and midbrain of 18.2 and 11.9 h, respectively. RISA was distributed in high concentration to subarachnoid arteries that supplied the tissue injection site; this was consistent with RISA drainage from brain via perivascular spaces. Outflow through lymph rose to a maximum value 15-20 h after tracer injection. Mean recovery of RISA from lymph over the 25-h collection period accounted for 22% of total loss from internal capsule and 18% from midbrain. This result compares with mean recoveries from caudate nucleus and cerebrospinal fluid of 47% and 30%, respectively [M.W.B. Bradbury, H.F. Cserr, and R.J. Westrop, Am. J. Physiol. 240 (Renal Fluid Electrolyte Physiol. 9): F329-F336, 1981]. These are minimal estimates of total outflow to lymph because of the 15- to 20-h delay in RISA passage from brain to lymph.