bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of tyrosine infusion in normotensive and hypertensive rats
Authors: Bresnahan M. R. , Hatzinikolaou P. , Brunner H. R. , Gavras H.
Published: December 2017

To clarify further the action of acute administration of L-tyrosine in lowering blood pressure, L-tyrosine ethylester was infused intravenously into awake [deoxycorticosterone acetate (DOCA)-salt] hypertensive rats, two-kidney Goldblatt hypertensive rats, and normotensive rats. The effects of tyrosine were measured on arterial pressure, heart rate, plasma catecholamine levels, and plasma renin activity. Blood pressure and heart rate were lowered in all groups despite significant elevation of plasma dopamine in all groups and epinephrine in the hypertensive groups, norepinephrine did not rise significantly, and plasma renin activity was always found to be within the ranges expected for each model. It was concluded that tyrosine produced the progressive decline in blood pressure and heart rate by bringing about a sustained state of parasympathetic dominance, as effective sympathetic compensation did not occcur. This could be attributed to increased alpha-adrenergic activity in certain sites in brain secondary to increased catecholaminergic activity in these areas.
A computer-controlled stimulator with applications to cardiac electrophysiology
Authors: Elharrar V.
Published: December 2017

A computer-controlled stimulator compatible with S-100 microcomputers using an 8080 or Z-80 microprocessor is described. The pusle interval is controlled from 1 to 65,535 ms and the pulse duration from 1 to 255 ms by steps of 1 ms. The pulse amplitude is controlled from 0 to 10.24 V (in constant voltage mode) and from 0 to 1 mA (in constant current mode) by steps of 4 mV and 4 mu A, respectively. The characteristics of the stimuli and their timing can be altered automatically according to programmed protocols that may or may not take into account the response of the biologic preparation. Applications of this stimulator to the study of experimental cardiac electrophysiology are illustrated in vivo and in vitro.
Mechanism of action of vasoactive intestinal polypeptide on cerebral arterioles
Authors: Wei E. P. , Kontos H. A. , Said S. I.
Published: December 2017

The effect of vasoactive intestinal polypeptide (VIP) on cerebral arterioles was examined in anesthetized cats equipped with an acutely implanted cranial window for the observation of the pial microcirculation. Topical application of VIP on the surface of the brain in doses of 0.01-1.0 microgram/ml produced a dose-related vasodilation that was of equal magnitude in small (< 100 micrometer diam) and large (> 100 micrometer diam) pial arterioles. The maximum dilation averaged 20% of the control diameter. There were no associated changes in arterial blood pressure or in arterial CO2 tension. In additional experiments the vasodilator effect of VIP was completely inhibited by pretreatment with intravenous indomethacin or AHR-5850. These nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase activity and thereby interfere with the synthesis of prostaglandins and related compounds. The vasodilator effect to topical histamine was unaffected by indomethacin and AHR-5850. The results show that VIP has a strong vasodilator effect on pial arterioles of the cat and suggest that this effect is mediated by prostaglandins.
Evidence for bradykinin potentiation by angiotensin congeners in conscious rats
Authors: Textor S. C. , Brunner H. , Gavras H.
Published: December 2017

It has become increasingly clear that the potent vasoactive peptides bradykinin and angiotensin share a common point of metabolism, i.e., angiotensin-converting enzyme or kininase II, and may interact with prostaglandins to regulate regional blood flow. To establish whether the sensitivity to exogenous bradykinin was affected by the presence of angiotensin, vasodepressor dose-response curves to injected bradykinin were performed in conscious rats before and during a 1-h infusion of angiotensin I (30 ng/min), angiotensin II (30 and 300 mg/min), and [Sar2,Ala8]angiotensin II (5 micrograms/min). All of these induced a parallel leftward shift of the bradykinin dose-response curve of approximately threefold. No similar changes were observed during control infusions of dextrose, similar pressor doses of lysine vasopressin, or norepinephrine. Sensitivity to bradykinin was enhanced by saralasin in normal and nephrectomized rats, suggesting that the antagonist itself was responsible. Similar potentiation was present during both acute (1 h) and chronic infusions (9 days) of angiotensin II and attenuated the effect of a converting-enzyme inhibitor on bradykinin sensitivity. Accordingly, these results suggest a competitive interaction in vivo between angiotensin congeners and bradykinin at a point of bradykinin degradation, probably angiotensin-converting enzyme or kininase II. This is a potential additional mechanism by which these systems may interact to affect regional blood flow and must be considered in the interpretation of results obtained during saralasin infusion.
Myocardial protection from ischemic arrest: potassium and verapamil cardioplegia
Authors: Pinsky W. W. , Lewis R. M. , McMillin-Wood J. B. , Hara H. , Hartley C. J. , Gillette P. C. , Entman M. L.
Published: December 2017

Prolonged normothermic myocardial ischemic arrest results in myocardial dysfunction. This study has investigated the technique of preserving myocardial function by a single bolus intracoronary infusion of combination potassium and verapamil at the onset of ischemic arrest. Sixty-one dogs underwent cardiopulmonary bypass with 60 min of ischemic arrest: 25 received no myocardial protection, 12 received a single intracoronary bolus of KCl, 12 received combination verapamil and KCl, and 12 received verapamil alone. Following the ischemic arrest, hearts protected by combination of potassium and verapamil demonstrated better survival evidenced by the ability of all 12 dogs to resume normal hemodynamic function. The hemodynamic function in the combination potassium and verapamil group also demonstrated better cardiac output, left ventricular dF/dt, and myocardial segment shortening than survivors in the other groups. Subsarcolemmal (SSL) and intermyofibrillar IMF) mitochondria were isolated from these hearts and function evaluated. NADH-linked oxygen consumption was impaired as was calcium transport in the SSL from unprotected ischemic hearts. Intermyofibrillar mitochondria were not different from control or sham. The hearts protected by verapamil and potassium demonstrated normal mitochondrial function.
Structural, functional, and metabolic correlates in ischemic hearts: effects of substrates
Authors: Feuvray D.
Published: December 2017

The ultrastructure, function, and metabolism of isolated rat hearts perfused under control or ischemic conditions were investigated. Either both glucose (11 mM) or glucose and palmitic acid (1.5 mM) were used as metabolic substrates. A 60-min period of whole-heart ischemia, i.e., a 60% initial reduction in coronary flow, resulted in a more dramatic morphological alteration in those hearts receiving palmitate compared to those receiving glucose as the only substrate. In ischemic hearts receiving palmitate, intramitochondrial osmiophilic amorphous densities of both rounded and elongated types were observed. These amorphous densities did not develop in ischemic hearts receiving glucose alone over the same period of ischemia. Such morphological alterations were associated with a more severe deterioration of mechanical function in the presence of palmitate. Both ischemic conditions resulted in increased tissue levels of acyl esters of CoA and carnitine, but the rise in levels of long-chain acyl carnitine was about two times greater in those ischemic hearts receiving palmitate.
Femoral circulatory responses to lumbar nerve stimulation in developing swine
Authors: Buckley N. M. , Brazeau P. , Frasier I. D. , Gootman P. M.
Published: December 2017

The maturation of femoral circulatory responses to efferent lumbar nerve stimulation was tested in 51 developing swine (1 day-3 mo old) under pentobarbital sodium anesthesia (10-30 mg/kg). Aortic pressure, heart rate, and femoral and carotid arterial flows (measured by electromagnetic flow transducers) were recorded simultaneously. Femoral vascular resistance was calculated as mean aortic pressure/mean flow. Transection of the lumbar nerve fibers below the last ganglion in the sympathetic chain did not after femoral resistance in day-old animals but decreased femoral resistance in swine 1 wk of age and older. Efferent lumbar nerve stimulation at various combinations of frequencies and intensities revealed an atropine-blockable vasodilator component in the femoral circulatory response in swine 1 mo of age and older. After alpha-adrenergic receptor blockade with phentolamine (0.25 or 0.5 mg/kg), femoral vasodilation occurred during low-frequency and -intensity stimulation of the lumbar nerve only in animals 1 mo of age and older. Acetylcholine (2 micrograms ia) caused a decrease in femoral resistance at all ages. Vasoconstrictor effects of high-frequency stimulation (5-10 Hz) were present at all ages and were age dependent. The results of these experiments suggest that the femoral circulation in swine at birth in innervated by functionally active vasoconstrictor fibers, which do not provide a tonic influence on femoral resistance until late in the first postnatal week. Furthermore, although femoral vascular cholinergic receptors are demonstrable at birth, there appears to be a delay in the maturation of functionally active vasodilator fibers.
Electrophysiological effects of insulin on normal and depressed cardiac tissues
Authors: LaManna V. R. , Ferrier G. R.
Published: December 2017

The electrophysiological effects of insulin were studied in canine false tendons (FT) and papillary muscles from kittens and rats. Insulin caused hyperpolarization (2-8 mV) and an increase in action potential (AP) amplitude. However, the rate of rise and duration of the AP, the slope of phase 4 depolarization and conduction velocity were unchanged in the normal tissues. In preparations depressed spontaneously or by stretch or low pH (6.7), hyperpolarization was larger than observed in normal tissues. Insulin partially normalized electrophysiological parameters under these conditions but not in the presence of anoxia (95% N2). The membrane resistances of normal canine FT and kitten papillary muscles were not changed by insulin. Blockade of K channels by CsCl doubled hyperpolarization induced by the hormone. Insulin effects were abolished by cold (21 degrees C), ouabain (3-9 X 10(-7) M), or acetylstrophanthidin (0.5-3 X 10(-6) M). Overdrive hyperpolarization was enhanced by insulin. These experiments suggest that insulin-induced hyperpolarization is mediated by activation of the electrogenic Na pump and not by a change in membrane conductance.
Multipoint pulmonary vascular pressure-cardiac output plots in conscious dogs
Authors: Lodato R. F. , Michael J. R. , Murray P. A.
Published: December 2017

To characterize quantitatively the relationships among pulmonary vascular pressures (P) and cardiac output (Q) in conscious dogs, multipoint plots of pulmonary arterial (PAP), pulmonary capillary wedge (PCWP), PAP - PCWP, and left atrial (LAP) pressure versus Q were generated by graded constriction of the thoracic inferior vena cava (IVC) to vary Q. Slopes and extrapolated pressure intercepts from linear regression fits to the P/Q plots were determined for three inspired oxygen tensions: normoxia, hyperoxia, and hypoxia. During normoxia (arterial Po2 87 +/- 1 Torr), the extrapolated pressure intercepts for PAP, PCWP, and PAP - PCWP were virtually 0 mmHg, and for LAP, substantially negative (-5.5 +/- 1.1 mmHg; P less than 0.01). Hyperoxia (Po2 365 +/- 28 Torr) had no effect on any of the P/Q plots. In contrast, hypoxia (Po2 51 +/- 1 Torr) significantly increased the intercepts (P less than 0.01) as well as the slopes (P less than 0.05) of PAP and PAP - PCWP versus Q, but produced only minor changes in PCWP and LAP versus Q. These hypoxia-induced changes in intercepts, perhaps related to changes in critical closing pressures, demonstrate the limitations of pulmonary vascular resistance calculations (quotient of pressure gradient and Q) in quantifying changes in pulmonary vasomotor tone. In this way, the IVC constriction technique provides a more complete description of P/Q relationships than that permitted by simple calculations of pulmonary vascular resistance. We conclude that this technique can be utilized to investigate the effects of other physiological and pharmacological interventions on pulmonary vasomotor tone in conscious dogs.
Evidence and quantitation of left ventricular systolic resistance
Authors: Shroff S. G. , Janicki J. S. , Weber K. T.
Published: December 2017

Instantaneous left ventricular pressure is a function of both volume (elastic behavior) and flow (resistive behavior). However, a quantitative description of ventricular resistance and its effects on ventricular performance remains to be elucidated. Accordingly, ventricular resistive behavior was studied in six isolated canine hearts. Our experimental findings indicate 1) for a specified time (ts), volume (Vs), and contractile state (CS), the ventricular pressure-flow relation was linear (r = 0.96-0.99) within the range of flows examined (0-250 ml/s); 2) ventricular resistance increased with increments in ts, Vs, and CS, whereas the zero-pressure flow intercept was invariant; 3) resistance could be uniquely quantified as a linear function of isovolumetric pressure. In six experiments, the slope of this relationship ranged from 1.1 to 2.1 X 10(-3) s/ml while the intercept did not differ from zero; and 4) end-systolic elastance, estimated from end-systolic pressure-volume data, was in substantial error under the conditions of finite (greater than 35 ml/s) end-systolic flows. Finally, the results from a computer simulation of the coupled ventricular-arterial system indicated that ventricular resistance primarily affects the pulsatile nature of aortic flow. The unique isovolumetric pressure-resistance relation suggests that the rate-limiting properties of the contractile process may be causally related to the observed ventricular resistive behavior.
Measurement of erythrocyte velocity by use of a periodic differential detector
Authors: Fleming B. P. , Klitzman B. , Johnson W. O.
Published: December 2017

An optical velocimeter employing a linear array of photodiodes has been developed and utilized for measuring erythrocyte velocities in the microcirculation. A magnified image of a microvessel is projected and aligned on a one-dimensional array of photodiodes. Photocurrent from odd-ordered diodes is summed, photocurrent from even-ordered diodes is summed, and a signal proportional to the difference between these two currents is produced by a differential amplifier. The center frequency of the output signal of the differential amplifier is proportional to the erythrocyte velocity. After lowpass filtering the output of the differential amplifier, a signal proportional to its frequency and therefore velocity is produced by a frequency-voltage converter. In vitro calibration with a moving dried smear of erythrocytes illustrated a linear relation between the output of the frequency-voltage converter and erythrocyte velocity for a wide range of velocities and magnifications. The system produces a stable zero output at zero velocity and had an estimated frequency response of greater than 40 Hz in vivo. Volumetric flow rates computed from velocity and diameter measurements at arteriolar bifurcations in the rat cremaster muscle were consistent with mass conservation.
Vasopressin dose-response effects on fetal vascular pressures, heart rate, and blood volume
Authors: Tomita H. , Brace R. A. , Cheung C. Y. , Longo L. D.
Published: December 2017

To determine the effects of circulating arginine vasopressin (AVP) on fetal arterial pressure, venous pressure, heart rate, and blood volume, we infused graded amounts of AVP into chronically catheterized fetal sheep at 122-136 days gestation (term 145-150 days). Plasma AVP concentrations increased by 6.5 +/- 3.9 (SE), 13.0 +/- 2.4, 55 +/- 11.7, and 144 +/- 42 pg/ml with infusion rates of 1, 3.3, 10, and 33 ng/min, respectively. Fetal arterial pressure rose 0, 7.2 +/- 1.0, 9.1 +/- 2.5, 11.4 +/- 2.9, and 12.1 +/- 2.4 mmHg while heart rate decreased 0, 24 +/- 5, 36 +/- 10, 59 +/- 9, and 62 +/- 9 beats/min during AVP infusions of 0.5, 3.3, 10, 33, and 700 ng/min, respectively. Fetal venous pressure was unchanged except that it increased 2.4 +/- 0.5 and 4.8 +/- 1.5 mmHg at infusion rates of 33 and 700 ng/min, respectively. Fetal blood volume remained unchanged except for a 7.2 +/- 3.4% decrease with 700 ng/min. After blockade of the fetal autonomic nervous system, the arterial pressure increase was twice and the heart rate decrease was one-third of those observed in autonomically intact fetuses with comparable AVP infusion rates. Thus these fetal cardiovascular variables showed differential sensitivity to increases in circulating AVP concentrations, suggesting that physiological variations in endogenous AVP may have short-term effects on fetal arterial pressure and heart rate, but probably not on venous pressure or blood volume.
Beta-adrenoceptor-mediated release of angiotensin II from mesenteric arteries
Authors: Nakamaru M. , Jackson E. K. , Inagami T.
Published: December 2017

Essential components of the renin-angiotensin system such as renin enzymes, angiotensinogen, converting enzyme, and angiotensin receptors have been found in vascular tissues. Locally generated angiotensin (ANG) II may regulate vascular tone by contracting vascular smooth muscle or potentiating sympathetic activity. Recently it was suggested that beta-adrenoceptor-induced enhancement of noradrenergic neurotransmission is mediated by the vascular renin-angiotensin system. The present study was designated to obtain direct evidence for the release of ANG II from the vasculature by beta-adrenoceptor activation. Isolated rat mesenteric arteries were perfused in vitro with Krebs-Ringer solution, and released ANG II was concentrated in a Sep-Pak C-18 cartridge connected to the perfusion system. High-pressure liquid chromatography combined with radioimmunoassay clearly demonstrated the presence of ANG I, II, and a small amount of ANG III in the perfusate. Isoproterenol (10(-9) - 10(-6) M) induced the enhancement of pressor responses to nerve stimulation. This effect was markedly suppressed by propranolol (5 X 10(-7) M), captopril (2 X 10(-6) M), or [Sar1-Ile8]ANG II (10(-6) M). Isoproterenol (10(-9) - 10(-6) M) caused increase in the release of ANG II from mesenteric arteries. The increase in ANG II release during isoproterenol (10(-6) M) infusion was blocked by propranolol (10(-6) M). Captopril (2 X 10(-6) M) also inhibited the increase in ANG II induced by isoproterenol. These results indicate that locally generated ANG II is released from isolated perfused rat mesenteric arteries and its release is mediated by beta-adrenoceptors.
Terminology for mass transport and exchange
Authors: Bassingthwaighte J. B. , Chinard F. P. , Crone C. , Goresky C. A. , Lassen N. A. , Reneman R. S. , Zierler K. L.
Published: December 2017

Virtually all fields of physiological research now encompass various aspects of solute transport by convection, diffusion, and permeation across membranes. Accordingly, this set of terms, symbols, definitions, and units is proposed as a means of clear communication among workers in the physiological, engineering, and physical sciences. The goal is to provide a setting for quantitative descriptions of physiological transport phenomena.
Antihypertensive effect of thyroidectomy in SHR: associated changes in heart performance
Authors: Rodgers R. L. , McNeill J. H.
Published: December 2017

Effects of thyroidectomy (TX; 10 wk) on the performance of perfused hearts from spontaneously hypertensive rats (SHR) were compared with effects on hearts from normotensive Wistar-Kyoto (WKY) controls. TX prevented the development of hypertension in SHR and moderately reduced arterial pressure of WKY, confirming previous observations. TX also reduced heart-to-body-weight ratio (relative left ventricular hypertrophy) but not left-to-right ventricular weight ratio (absolute hypertrophy) of SHR. The performances of euthyroid SHR and WKY hearts were similar to each other. TX reduced maximum left ventricular pulse pressure to the same extent in both strains and had no effect on hydraulic work, O2 consumption, or efficiency of contraction in either strain. However, TX reduced maximum left ventricular +dP/dt of SHR but not of WKY hearts. The results show that hypothyroidism selectively depresses the contractility (LV +dP/dt) of SHR hearts but otherwise has similar effects on the performance of hypertensive and normotensive rat hearts.
Electrophysiological properties of cultured adult rat ventricular cardiac muscle cells
Authors: Meier C. F. , Briggs G. M. , Claycomb W. C.
Published: December 2017

Action and resting potential characteristics of isolated adult rat myocardial cells maintained in culture for 10–28 days are described. Resting potentials averaged -76.3 +/- 2 mV in 5 mM extracellular [K+] ([K+]o). Resting potentials changed by 54.3 mV/decade change in [K+]o for concentrations greater than 5 mM. The average maximum rate of rise of action potential (Vmax) was 117.7 +/- 10 V/s with overshoots of 34.6 +/- 2.5 mV. Action potential durations (APD) to 0 and -40 mV and full repolarization were 21.8 +/- 3.9, 36.3 +/- 6.0, and 206 +/- 16.9 ms respectively. Action potential configurations were qualitatively similar to those previously reported by others for rat myocardial tissue or freshly dissociated cells. Tetrodotoxin (4 micrograms/ml) decreased Vmax to less than 24 V/s and decreased overshoot and APD. Isoproterenol (10(-8) M) decreased APD with slight elevation of the overshoot. Verapamil (10(-5) to 10(-4) M) depressed overshoot and plateau while slowing the final phase of repolarization. Verapamil (10(-4) M) depressed upstroke velocity and blocked excitability. While APDs recorded from these cultured cells are apparently longer than those reported by others for rat myocardial APDs, the values of all other electrophysiological parameters recorded are within the limits previously reported for normal rat myocardial tissue. These data indicate that adult rat myocardial cells maintained in tissue culture for 10–28 days possess electrophysiological properties and responses to pharmacological agents similar to adult rat myocardial tissue or undamaged freshly isolated cells.
Effects of halothane on transmembrane potentials, Ca2+ transients, and papillary muscle tension in the cat
Authors: Bosnjak Z. J. , Kampine J. P.
Published: December 2017

The effects of halothane on cat papillary muscle were studied in vitro at different pacing rates (60, 75, 100, and 150 beats/min). Simultaneous measurements of transmembrane potentials, intracellular Ca2+ transients, and isometric tension were made before and after introduction of 1 and 2 minimal alveolar concentration halothane. Anesthetic concentrations in the superfusion bath were measured using a gas chromatography procedure. The Ca2+-sensitive photoprotein, aequorin, was microinjected into papillary muscle cells. Aequorin light emission is a function of free intracellular [Ca2+] [( Ca2+]i). The most prominent effects of halothane were a dose-dependent decrease in the contractile force and a decrease in [Ca2+]i, at all pacing rates. The negative inotropic effect of halothane was associated with only small changes in the papillary muscle action potential duration. Increasing the extracellular [Ca2+] produced an increase in [Ca2+]i and counteracted the negative inotropic effects of halothane. Addition of the Ca2+ channel blocker, verapamil, and halothane, produced an additive decrease in [Ca2+]i compared with the control.
Phasic effects of postganglionic vagal stimulation on atrioventricular nodal conduction
Authors: Mazgalev T. , Dreifus L. S. , Michelson E. L. , Pelleg A. , Price R.
Published: December 2017

The effects of postganglionic vagal stimulation (PGVS) on atrioventricular nodal conduction were studied in 15 rabbit atrial-atrioventricular nodal preparations. PGVS was introduced, and sinus cycle length was scanned as independent bursts of subthreshold stimuli were produced in the sinus node and atrioventricular node (AVN). Changes in conduction of atrial impulses to the bundle of His were studied under the following experimental conditions: changes in sinus cycle length resulting from vagal influence on the sinus node, direct vagal stimulation exclusively to the AVN, and during both simultaneous or nonsimultaneous vagal stimulation to sinus node and AVN. The results of the present study showed that the direct effect of PGVS on AVN conduction time at a constant sinus cycle length is phase dependent with maximal prolongation achieved in the first or second beat after introduction of the burst. The interval between the onset of PGVS producing maximal prolongation of conduction time and the following atrial beat was designated the "optimal effective phase." It was shown that the optimal effective phase was a constant parameter for a given preparation and in the present experiments was 321 +/- 16 ms. However, when PGVS was introduced in combination to both nodes while scanning the cycle length, AVN conduction was variable, reflecting both the direct effects of PGVS on the AVN as well as the indirect effects resulting from changes in the sinus cycle length. Notably, it was found that simultaneous PGVS to both the sinus node and AVN usually diminished, whereas appropriate nonsimultaneous PGVS accentuated the typical phasic dependency of AVN conduction time. Additionally, vagally induced prolongation of the sinus cycle length was found to be accompanied by changes in the time of depolarization of the inputs to the AVN, thus influencing AVN conduction and facilitating reentry. These interactions between changes in the sinus cycle length and concomitant changes in the effectiveness of vagal influence on the AVN can be used to explain complexities of AVN conduction during increased vagal activity.
Sites at which vasopressin facilitates baroreflex inhibition of lumbar sympathetic nerve activity
Authors: Guo G. B. , Schmid P. G. , Abboud F. M.
Published: December 2017

We recently reported that intravenous vasopressin in anesthetized rabbits facilitates baroreflex inhibition of lumbar sympathetic nerve activity. The purpose of this study was to determine the possible sites of this facilitation. We found that intravenous infusion of vasopressin (16-32 mU X kg-1 X min-1) caused greater inhibition of lumbar sympathetic nerve activity than did phenylephrine for a given increase in aortic baroreceptor activity, suggesting a "central" action of vasopressin. A central action was supported also by the observation that the carotid baroreflex inhibition of lumbar sympathetic nerve activity was augmented by intravenous infusion of vasopressin when the carotid sinuses were isolated, filled with saline, and distended (aortic depressor and vagal nerves were cut). On the other hand, vasopressin also facilitated baroreflex inhibition of lumbar sympathetic nerve activity through an influence on arterial baroreceptors, because intravenous vasopressin caused greater afferent activity of the aortic depressor nerve per unit rise in arterial pressure than did phenylephrine. In a separate group of rabbits, intravenous infusion of vasopressin also elevated the level of afferent aortic depressor activity during increases in arterial pressure induced by intra-aortic balloon inflation. Furthermore, when vasopressin was confined to the isolated carotid sinuses, the reflex inhibition of lumbar sympathetic nerve activity during distension of carotid sinuses was augmented. We conclude that circulating vasopressin facilitates baroreflex inhibition of sympathetic nerve activity through a central nervous system action as well as through an effect on arterial baroreceptors.
Age-related responses to stimulation of cardiopulmonary receptors in swine
Authors: Gootman P. M. , Buckley B. J. , DiRusso S. M. , Gootman N. , Yao A. C. , Pierce P. E. , Griswold P. G. , Epstein M. D. , Cohen H. L. , Nudel D. B.
Published: December 2017

Cardiovascular responses to stimulation of cardiopulmonary receptors were evaluated in standard breed developing swine (1-2 days, 1-2 wk, and 2 mo of age) and sexually mature miniswine anesthetized with 0.25-0.50% halothane in O2. Cryptenamine, a mixture of veratrum viride alkaloids (VVA), was administered as right atrial or left ventricular bolus injections in doses of 5-20 micrograms/kg. In developing swine, mean aortic pressure (AoP) decreased after 10-20 micrograms/kg VVA in 1- to 2-wk olds and after 5-20 micrograms/kg VVA in 2-mo olds. Bradycardia was always elicited. Renal (Ren) and femoral (Fem) vasodilation occurred in the 1- to 2-wk-old and 2-mo-old groups after 5-20 micrograms/kg VVA. Mesenteric (Mes) vasodilation was elicited with 10-20 micrograms/kg VVA in the 1- to 2-wk-old group and with 5-20 micrograms/kg VVA in 2-mo olds. In the 1- to 2-day-old group, VVA did not significantly alter Ren, Fem, and Mes vascular resistance. In mature miniswine, 20 micrograms/kg VVA elicited decreases in AoP and heart rate that were similar in magnitude to responses obtained with only 5 micrograms/kg VVA in dogs. Cardiovascular responses to VVA were abolished after bilateral vagotomy but were not altered after denervation of the carotid sinuses. The results indicate postnatal maturation of the Bezold-Jarisch reflex in swine.
Neurovascular function in the rat during pregnancy
Authors: Hart J. L. , Freas W. , Muldoon S. M.
Published: December 2017

Activity of the vascular neuroeffector junction was examined in pregnant (PG) and nonpregnant (NPG) rats to determine whether changes could account for the reported alterations in sympathetic control of the maternal circulation. Caudal and mesenteric arteries were removed from NPG and 19-21 day PG rats and prepared for isometric tension recording. Frequency-response measurements were obtained, followed by norepinephrine (NE) and tyramine concentration-response measurements. The caudal artery developed more tension in response to NE, tyramine, and electrical stimulation than did the mesenteric artery; however, there were no differences between vessels from NPG and PG rats. NE content, [3H]NE accumulation, and effects of plasma on [3H]NE accumulation of NPG and PG caudal arteries were also compared and found to be similar. Therefore, vascular neuroeffector functions of NE release, receptor sensitivity, and NE accumulation are not modified in the rat during pregnancy. Changes in sympathetic control of the maternal circulation are likely to be dependent on alterations at sites other than the neuroeffector junction.
Regional sciatic nerve and muscle blood flow in conscious and anesthetized rats
Authors: Sugimoto H. , Monafo W. W. , Eliasson S. G.
Published: December 2017

The regulation of peripheral nerve blood flow is incompletely understood. Regional blood flow in the rat sciatic nerve (NBF) and hamstring muscle (MBF) was measured in both conscious and anesthetized normal rats and in rats that had undergone surgical exposure of one sciatic nerve just prior to measurement. The distribution of [14C]butanol following its bolus intravenous injection was used to determine the flows in a modification of the “indicator fractionation” technique. NBF in normal rats was similar in limb pairs and was unaffected by pentobarbital sodium anesthesia. The pooled value was 12.5 +/- 1.1 ml X min-1 X 100 g-1. NBF was unaffected by sham operation in the conscious rats but was doubled in operated limbs of anesthetized rats (P less than 0.001). MBF in conscious normal rats was five times that measured during anesthesia. As in NBF, sham operation significantly increased MBF only in anesthetized rats (P less than 0.01). [14C]butanol distribution is a sensitive indicator of NBF and MBF. Mere surgical exposure of the nerve significantly increases NBF and MBF in anesthetized, but not in conscious rats.
Cardiovascular actions of vasopressin: baroreflex modulation in the conscious rat
Authors: Webb R. L. , Osborn J. W. , Cowley A. W.
Published: December 2017

Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were recorded during graded infusions of arginine vasopressin (AVP), angiotensin II (ANG II), and phenylephrine (PE) in conscious, unrestrained, sinoaortic-denervated (SAD) and normal rats. Base-line MAP, CO, and TPR values before infusion were not different between groups. HR values were significantly higher in SAD rats. Dose-response curves indicated that there was a similar enhancement in pressor sensitivity to AVP, ANG II, and PE in the absence of the baroreceptors. Pressor responses to AVP were buffered by offsetting decreases of CO. Similar elevations in MAP evoked a 50% greater reduction in CO with AVP, and HR decreased 1.5 times as much with AVP than with ANG II or PE. The dose of AVP required to raise MAP by 25 mmHg in control rats resulted in similar falls of CO in SAD rats, whereas HR responses to AVP were attenuated significantly in SAD rats. We conclude that baroreceptor buffering of AVP-induced pressor responses is due principally to reflex reduction of TPR. Furthermore, CO suppression was not baroreflex-mediated, whereas bradycardia was reflex dependent. Finally, in rats, AVP does not appear to interact with the baroreceptor reflexes in a manner unique from other vasoconstrictor agents to buffer MAP.
Role of vasopressin in the cardiovascular response to hypoxia in the conscious rat
Authors: Walker B. R.
Published: December 2017

Previous experiments have demonstrated that hypoxia stimulates the release of arginine vasopressin in conscious animals including the rat. The present study was designed to test whether AVP may exert a vasoconstrictor influence during hypoxia at varying levels of CO2. Systemic hemodynamics were assessed in conscious rats for 30 min under hypocapnic hypoxic, isocapnic hypoxic, hypercapnic hypoxic, and room air conditions. Progressive effects on heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were observed with varying CO2 under hypoxic conditions. Hypocapnic hypoxia [arterial PO2 (PaO2) = 32 Torr; arterial PCO2 (PaCO2) = 22 Torr] caused HR and CO to rise and TPR to fall. Isocapnic hypoxia (PaO2 = 36 Torr; PaCO2 = 35 Torr) was associated with no significant changes in HR and CO or TPR, whereas hypercapnic hypoxia (PaO2 = 35 Torr; PaCO2 = 51 Torr) caused HR and CO to fall and TPR to rise. Room air time control experiments were associated with no change in measured hemodynamic variables. To determine the possible role of circulating AVP on these cardiovascular responses, additional experiments were performed where the specific V1-vasopressinergic antagonist d(CH2)5Tyr(Me)AVP (10 micrograms/kg iv) was administered at the midpoint of hypoxic exposure. Antagonist administration had no effect on hypocapnic hypoxic animals or animals breathing room air; however, blood pressure and TPR were significantly reduced by d(CH2)5Tyr(Me)AVP in both isocapnic and hypercapnic hypoxic animals. The heart rate response to hypoxia at the various CO2 levels was unaffected; however, cardiac output and stroke volume were increased after V1-antagonism in the isocapnic and hypercapnic hypoxic animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary edema in dogs fails to cause reflex responses
Authors: Wead W. B. , Cassidy S. S. , Reynolds R. C.
Published: December 2017

Pulmonary edema has been proposed as a stimulus for pulmonary C-fibers. Stimulation of pulmonary C-fibers causes depression of cardiovascular function and either tachypnea or apnea. Our objective was to determine whether pulmonary edema, induced by either increasing pulmonary vascular permeability with alloxan or hydrostatic challenges, would elicit depression of cardiovascular function or changes in frequency of inspiratory activity. Utilizing a preparation in which the left pulmonary vessels and left airway were isolated, we monitored systemic blood pressure (BP), heart rate (HR), and diaphragm contractions (DC) in 13 anesthetized dogs. Injection of alloxan into the left pulmonary artery (LPA) produced transient decreases in HR, BP, and frequency of DC within 20 s of injection with no subsequent cardiorespiratory changes up to 5 min. These alloxan injections also caused coagulation necrosis. Generation of hydrostatic pulmonary edema in the left lung caused no changes in HR, BP, or in the frequency and amplitude of DC. We conclude that alloxan does stimulate reflex cardiorespiratory depression consistent with C-fiber stimulation, but these reflex responses are probably caused by alloxan's caustic effect and not by the resultant edema. We also conclude that pulmonary edema induced by increased hydrostatic pressure does not evoke any reflex cardiovascular responses or changes in frequency of inspiratory activity.
NO synthesis is involved in structural and functional effects of ACE inhibitors in injured arteries
Authors: Van Belle E. , Vallet B. , Auffray J. L. , Bauters C. , Hamon M. , McFadden E. P. , Lablanche J. M. , Dupuis B. , Bertrand M. E.
Published: December 2017

Angiotensin-converting enzyme (ACE) inhibitors reduce intimal hyperplasia after balloon injury. A role for nitric oxide (NO) has been suggested in this effect. Because recent data suggest that NO may modulate some features of endothelial cells and because endothelial cells are involved in the control of intimal hyperplasia, we investigated the role of NO synthesis in the effect of an ACE inhibitor, perindopril, on neoendothelial dysfunction and intimal hyperplasia in a rabbit model of unilateral iliac balloon injury. New Zealand White male rabbits received placebo, perindopril, or cotreatment with perindopril and NG-nitro-L-arginine methyl ester (L-NAME) and were evaluated 4 wk after the injury. Fifteen rabbits (5 in each group) were used to assess in vitro vasoreactivity and twenty-four (8 in each group) for morphometric analysis. In injured vessels, neoendothelium-dependent relaxation in ACE inhibitor-treated animals was improved compared with placebo (P < 0.05) and restored to the level of noninjured vessels (NS). The improvement observed with ACE inhibitor was abolished by cotreatment with L-NAME (P < 0.05). In the same vessels, no effect was observed on neoendothelium-independent vasoreactivity. The improved neoendothelial dysfunction with ACE inhibitor was associated with a 66% reduction in intimal thickening (P < 0.01). The effect was also reversed by cotreatment with L-NAME (P < 0.01). In noninjured vessels, treatment did not alter vasoreactivity or morphology of the vessel wall. These results suggest that NO synthesis may play a key role in the improvement of vascular function seen with ACE inhibitor in balloon-injured vessels.
Influence of graft innervation on neovascularization of embryonic heart tissue grafted in oculo
Authors: Torry R. J. , Rongish B. J. , Tucker D. C. , Kostreva D. R. , Tomanek R. J.
Published: December 2017

We have shown that sympathetic denervation increases subendocardial capillarity during left ventricular hypertrophy. To determine the direct effects of sympathetic innervation on development of the coronary microvasculature in the absence of hemodynamic load, we grafted avascular fetal rat atrial or ventricular tissue into the anterior eye chamber of host rats which had undergone unilateral superior cervical gangliectomies. Innervation to the contralateral eye chamber remained intact. The grafts were harvested 14 or 35 days later, and volume densities of blood vessels, myocytes, and extracellular matrix were determined using standard point-counting techniques on low-power electron micrographs. Graft perfusion and metabolism were assessed simultaneously with thallium-201 and 2-[14C]deoxy-D-glucose uptake, respectively. Innervation did not significantly alter the vascular volume densities or cellular composition of atrial or ventricular tissue compared with noninnervated tissue after either 14 or 35 days in oculo. Similarly, innervation did not significantly alter graft perfusion or metabolism. We conclude that sympathetic innervation does not directly influence the growth of the microvasculature or myocardial metabolism in hemodynamically unloaded, developing heart tissue.
Shear stress is not sufficient to control growth of vascular networks: a model study
Authors: Hacking W. J. , VanBavel E. , Spaan J. A.
Published: December 2017

Local vessel wall shear stress is considered to be important for vessel growth. This study is a theoretical investigation of how this mechanism contributes to the structure of a vascular network. The analyses and simulations were performed on vascular networks of increasing complexity, ranging from single-vessel resistance to large hexagonal networks. These networks were perfused by constant-flow sources, constant-pressure sources, or pressure sources with internal resistances. The mathematical foundation of the local endothelial shear stress and vessel wall adaptation was as follows: delta d/delta t = K*(tau-tau desired)*d, where d is vessel diameter, tau desired is desired shear stress, and K is a growth factor. Single vessels and networks with vessels in series developed stable optimal diameters when perfused at constant flow or with a constant-pressure source with internal resistance. However, when constant-pressure perfusion was applied, these vessels developed ever-increasing diameters or completely regressed. In networks with two vessels in parallel, only one; vessel attained an optimal diameter and the other regressed, irrespective of the nature of the perfusion source. Finally, large hexagonal networks regressed to a single vessel when perfused with a pressure source with internal resistance. The behavior was independent of variation in parameters, although the adaptation rate and the diameter of the final vessel were altered. Similar conclusions hold for models of vascular trees. We conclude that the effect of shear stress on vascular diameter alone does not lead to stable network structures, and additional factor(s) must be present.
Reducing lactate accumulation does not attenuate lethal ischemic injury in isolated perfused rat hearts
Authors: Vander Heide R. S. , Delyani J. A. , Jennings R. B. , Reimer K. A. , Steenbergen C.
Published: December 2017

The role of lactate accumulation in lethal ischemic myocardial cell injury was assessed by partially depleting hearts of glycogen before ischemia by using glucagon. Isolated adult rat hearts were perfused with glucose-free Krebs-Henseleit buffer containing acetate as substrate. After stabilization, treated hearts were perfused briefly (3 min) with buffer containing 2 micrograms/ml glucagon to reduce tissue glycogen stores, followed by 10 min of perfusion with control buffer, and 60 or 90 min of global ischemia. Before the onset of ischemia, glucagon-treated hearts contained 40% less glycogen than untreated hearts, but myocardial function and tissue levels of high-energy phosphates, lactate, and glucose 6-phosphate were similar. Lactate production during ischemia in the glucagon-treated hearts was 50% less than in untreated hearts. However, there was no decrease in the amount of creatine kinase release during reperfusion after either 60 or 90 min of ischemia. Thus although partial glycogen depletion reduced lactate accumulation during ischemia, this did not decrease the amount of lethal myocardial cell injury.
CARBON DIOXIDE PRODUCTION FROM NERVE FIBRES WHEN RESTING AND WHEN STIMULATED; A CONTRIBUTION TO THE CHEMICAL BASIS OF IRRITABILITY
Authors: Tashiro Shiro
Published: December 2017

in June number of the American Journal of Physiology (Vol. XXXII., No. II).

Substitute " apparatus" for " apparati" in the following places:

page 110, lines 7, 11, 23.

page 129, line 1.

page 137, line 28.

page 138, lines 1, 3.

page 144, line 6.

Substitute " 7.1 c.c." for " 1.1 c.c." on page 144, line 29.

In figure 1, page 120, correct as indicated the following drawing:

(See PDF)
INITIAL AND RECOVERY HEAT PRODUCTION IN SMOOTH MUSCLE BASED UPON EXPERIMENTS ON A URINARY BLADDER-NERVE PREPARATION FROM TERRAPIN
Authors: Snyder C. D. , Light F. W.
Published: December 2017

[ To be inserted by the binder in Volume 86, no. 2, of This Journal, and between pages 398 and 399.]

1. On page 399 add to the name of the co-author, "F. W. Light. Jr.," an asterisk, and at the bottom of the page add this footnote: "* Aided by a grant from The Henry Strong Denison Medical Foundation."

2. On page 414 in the first line of the legend change "iv" to "vi."

3. On page 417 in the seventh line from the bottom change the figure, "22.2" to "37.3."
THE INFLUENCE OF FREQUENCY OF CONTRACTION OF THE ISOLATED MAMMALIAN HEART UPON THE CONSUMPTION OF OXYGEN
Authors: Cohn A. E. , Steele J. Murray
Published: December 2017

On page 654 (3 lines from bottom) for (cf. 3. Table 111, p. 259) read (cf. Table III, p. 259).

On page 655 (first line) for (Table 4, p. 259) (3) read (Table IV, p. 259) ( 5).
Surgical reduction of adipose tissue in the male Sprague-Dawley rat
Authors: Kral JG
Published: December 2017

The lipostatic theory of regulation of adipose tissue mass was tested by a method for surgical reduction (adipectomy) of 24% of the total body fat of nonobese adult Sprague-Dawley rats, as judged from carcass analyses. The reduction persisted during an observation period of 12 wk without any evidence of altered food intake, weight gain, or compensatory hypertrophy or hyperplasia of adipose tissue compared with sham-operated controls. No changes were found in serum free fatty acids, glycerol, triglycerides, cholesterol, or insulin between adipectomized and control animals, implying an intact quantitative function of the remaining adipose tissue. It is concluded that the size of the adipocytes rather than the number is important for a presumed lipostatic regulation of adipose tissue mass in the adult male Sprague-Dawley rat.
Hereditary variation in uric acid transport by avian kidney slices
Authors: Austic RE , Cole RK
Published: December 2017

Uric acid transport in renal cortical slices from a selected line of hyperuricemic chickens was investigated. Slices from the hyperuricemic (HUA) line accumulated less than half as much uric acid as slices from a control (LUA) line when uric acid in the medium varied from 0.01 to 5 mM. Uric acid uptake by both lines increased as the uric acid concentration in the medium was raised from 0.1 to 0.5 mM, but was markedly inhibited in the HUA line at 3-5 mM. Omission of sodium or potassium from the incubation medium inhibited uric acid uptake by slices from both lines. Ouabain inhibited uric acid uptake in the LUA line. The sodium and potassium requirements for initiation of uric acid uptake were higher, and the potassium requirement for maximal uptake was lower, for slices of the HUA line. No genetic differences in potassium or sodium contents of slices were observed when the potassium content of the incubation medium was altered or when the medium contained ouabain. These studies indicate that hereditary hyperuricemia in chickens may be due to a qualitative change in renal uric acid transport which involves the interaction of cations in the transport process.
Inhibition of inotropic effect of hyperosmotic mannitol by lactate in vitro
Authors: Crie JS , Wildenthal K , Adcock R , Templeton G , Willerson JT
Published: December 2017

Isolated, isometrically contracting cat papillary muscles were used to evaluate the inotropic interactions of lactic acidosis, hypercarbic acidosis, and lactate ion with hypertonic mannitol. These studies have documented that both lactic acidosis (pH less than 7.0) and lactate ion at a normal pH inhibit the inotropic effect of hyperosmotic mannitol in vitro. In contrast, hypercarbic acidosis does not prevent the inotropic effect of mannitol. Inhibition by lactic acid of mannitol's effects on contractility persists in the presence of beta-receptor blockade. The results suggest that inhibition by severe lactic acidosis of the direct inotropic effect of hyperosmolality in isolated cardiac muscle is mediated by lactate ion rather than acidosis per se.