bluuebunny/crossref_metadata_2025 huggingface dataset:
Myogenic responses of isolated arterioles: test for a rate-sensitive mechanism
Authors: Davis M. J. , Sikes P. J.
Published: December 2017

The arterial myogenic response may consist of both static- and rate-sensitive components. However, in a recent study of bat wing arterioles, we were unable to demonstrate rate-sensitive constrictions when luminal pressure was elevated at rates between 0.06 and 1 mmHg/s. We have now examined this response in isolated arterioles in vitro, where pressure could be elevated more rapidly. Arterioles were dissected from the hamster cheek pouch and cannulated with micropipettes. Diameters were measured using an inverted microscope and video system, while the vessels were pressurized at various rates (up to 120 cmH2O/s) without flow. Most arterioles developed spontaneous tone and vasomotion and showed myogenic responses over the pressure range 40-160 cmH2O. The magnitude and time course of the active diameter response to a rapid pressure change was highly dependent on the amplitude and direction of the pressure step; monophasic constrictions were observed in response to small-amplitude, positive-pressure steps, and biphasic constrictions were consistently observed when box pressure was elevated to values exceeding 120 cmH2O. The time courses of these responses could be partially, but not completely, explained by a myogenic mechanism with static- and rate-sensitive components. The possible mechanism and physiological significance of this behavior in a microvascular network are discussed.
Effect of adrenal hypotension on elicited secretory activity in anesthetized dogs
Authors: Breslow M. J. , Tobin J. R. , Kubos K. L. , Raff H. , Traystman R. J.
Published: December 2017

The objective of this study was to determine whether three- to fourfold increases in adrenal medullary blood flow (MQ), observed during catecholamine secretion induced by splanchnic nerve stimulation (NS), are necessary for a maximal secretory response. Eight pentobarbital-anesthetized adult male mongrel dogs (25-35 kg) were subjected to two episodes of NS-induced catecholamine secretion. To limit increases in MQ, one NS (20 Hz, 8 V, 1.5 ms) was performed under control conditions, the other was after reduction of adrenal perfusion pressure (PP). PP was 124.8 +/- 6.0 at control and was reduced to 23.0 +/- 1.0 mmHg by inflation of an aortic occluder located 3 in. above the adrenals. NS under control conditions increased ipsilateral MQ (measured using radiolabeled microspheres) from 181 +/- 39 to 1,336 +/- 199 ml.min-1.100 g-1 and adrenal epinephrine secretion from 184 +/- 128 to 11,445 +/- 5,216 ng.min-1.g medulla-1. Contralateral MQ and cortical blood flow were unaffected by NS. Reduction of PP decreased MQ to 32 +/- 6 ml.min-1.100 g-1 and adrenal cortical blood flow from 251 +/- 23 to 25 +/- 6 ml.min-1.100 g-1.PP reduction had no effect on either corticosteroid secretion or unstimulated epinephrine secretion. NS at reduced PP increased ipsilateral MQ to 146 +/- 27 ml.min-1.100 g-1 and epinephrine secretion to 13,935 +/- 5,175 ng.min-1.g medulla-1. These data indicate that epinephrine secretion is not altered when MQ is limited by reduction of PP and suggest that, at normal PP, increases in MQ during catecholamine secretion are not necessary for a maximal secretory response.(ABSTRACT TRUNCATED AT 250 WORDS)
Carotid baroreceptor control of liver and spleen volume in cats
Authors: Maass-Moreno R. , Rothe C. F.
Published: December 2017

We tested the hypothesis that the blood volumes of the spleen and liver of cats are reflexly controlled by the carotid sinus (CS) baroreceptors. In pentobarbital-anesthetized cats the CS area was isolated and perfused so that intracarotid pressure (Pcs) could be controlled while maintaining a normal brain blood perfusion. The volume changes of the liver and spleen were estimated by measuring their thickness using ultrasonic techniques. Cardiac output, systemic arterial blood pressure (Psa), central venous pressure, central blood volume, total peripheral resistance, and heart rate were also measured. In vagotomized cats, increasing Pcs by 100 mmHg caused a significant reduction in Psa (-67.8%), cardiac output (-26.6%), total peripheral resistance (-49.5%), and heart rate (-15%) and significantly increased spleen volume (9.7%, corresponding to a 2.1 +/- 0.5 mm increase in thickness). The liver volume decreased, but only by 1.6% (0.6 +/- 0.2 mm decrease in thickness), a change opposite that observed in the spleen. The changes in cardiovascular variables and in spleen volume suggest that the animals had functioning reflexes. These results indicate that in pentobarbital-anesthetized cats the carotid baroreceptors affect the volume of the spleen but not the liver and suggest that, although the spleen has an active role in the control of arterial blood pressure in the cat, the liver does not.
Inhibition by cocaine of excitation-contraction coupling in isolated cardiomyocytes
Authors: Stewart G. , Rubin E. , Thomas A. P.
Published: December 2017

The effects of cocaine on the Ca2+ fluxes responsible for excitation-contraction coupling were studied in isolated ventricular rat heart cells loaded with the fluorescent Ca2+ indicator fura-2. Ca2+ transients in response to electrical field stimulation were followed using a fluorescence ratio method in which excitation light was alternated with 5-ms resolution. The cardiomyocytes maintained a basal cytosolic Ca2+ concentration of approximately 70 nM, which increased to a peak of 450 nM in response to each electrical stimulus. The addition of cocaine (10 microM) to cells stimulated at 0.4 Hz decreased the magnitude of the electrically induced Ca2+ transients by 30 +/- 4% within 5 s. This inhibitory effect of cocaine was dose dependent, with a 50% reduction in the Ca2+ transient occurring at 40 microM cocaine. The effects of cocaine were not associated with any permanent cell damage and could be reversed by washing the cells free of the drug. Cytosolic Ca2+ increases in response to K(+)-induced depolarization of the cardiomyocytes were much less sensitive to cocaine than the electrically induced Ca2+ transients. In this respect the effects of cocaine were similar to the actions of lidocaine and tetrodotoxin but distinct from the effects of nitrendipine and verapamil. Cocaine had no effect on the caffeine-releasable Ca2+ pool in cardiomyocytes. These data demonstrate that cocaine directly inhibits the Ca2(+)-dependent steps of excitation-contraction coupling in heart muscle cells. Sarcolemmal Na+ channels represent a possible locus for this action of cocaine.
Role of increased alpha 1-adrenergic activity in cardiomyopathic Syrian hamster
Authors: Kagiya T. , Hori M. , Iwakura K. , Iwai K. , Watanabe Y. , Uchida S. , Yoshida H. , Kitabatake A. , Inoue M. , Kamada T.
Published: December 2017

We investigated serial changes in myocardial norepinephrine content and myocardial adrenergic receptors during the development of cardiomyopathy in Syrian hamsters (Bio 14.6) and their age-matched healthy controls. We also examined phosphatidylinositide hydrolysis after alpha 1-adrenergic stimulation and the effects of alpha 1-blockade. We found that in the prehypertrophic stage, myocardial norepinephrine content and densities of alpha 1- and beta-adrenergic receptors were significantly higher in the cardiomyopathic hamsters than in the controls. However, in the early heart failure stage, beta-receptor density was 28% lower than that of the age-matched controls, although alpha 1-receptor density remained 55% higher. Norepinephrine-stimulated phosphatidylinositide hydrolysis in the cardiomyopathic hamster in the hypertrophic stage was twice that in the controls, indicating that the increase in alpha 1-adrenergic receptors is coupled with the intracellular signal transduction. Furthermore, selective alpha 1-adrenoceptor blockade by bunazosin in the cardiomyopathic hamsters from 70 to 170 days of age reduced myocardial hypertrophy and focal myocardial necrosis. Thus we conclude that increased alpha 1-adrenergic activity plays an important role in progression of cardiac hypertrophy is cardiomyopathic Syrian hamsters.
Human platelet aggregation and shape change are coupled to separate thromboxane A2-prostaglandin H2 receptors
Authors: Dorn G. W. , DeJesus A.
Published: December 2017

The relationships of human platelet thromboxane A2-prostaglandin H2 (TxA2/PGH2) receptor occupation as assessed by equilibrium binding of the TxA2/PGH2 agonist [125I]BOP to the functional responses of I-BOP-induced platelet shape change and aggregation were determined before and after specific, irreversible inactivation of platelet TxA2/PGH2 receptors with the photolyzable TxA2/PGH2 antagonist I-PTA-PON3. I-BOP stimulated platelet shape change and aggregation with concentrations producing a half-maximal response of 173 +/- 39 pM (n = 4) and 1.8 +/- 0.4 nM (n = 6), respectively (means +/- SE). Covalent inactivation of TxA2/PGH2 receptors with I-PTA-PON3 caused rightward shifts of I-BOP shape change and aggregation dose-response curves and resulted in pharmacological dissociation constants (Kd) of 134 pM and 1.95 nM, respectively. Isotherms of [125I] BOP binding to intact platelets (n = 6) were shallow with Hill coefficients of -0.68 +/- 0.03 and were best described by a two-site model with 222 +/- 58 sites/platelet of high affinity (Kd = 270 +/- 60 pM) and 818 +/- 90 sites/platelet of lower affinity (Kd = 3.9 +/- 1.2 nM). The relationship of I-BOP occupancy of high-affinity receptors to shape-change responses was linear (r = 0.97, P less than 0.001), but the occupancy-response relationship for the lower affinity receptor and platelet aggregation was hyperbolic with half-maximal aggregation occurring after occupation of 25% of the receptors. After covalent inactivation of a variable proportion of the receptors with I-PTA-PON3, the occupancy-response relationship for platelet aggregation resulted in a similar hyperbola indicating an excess of low-affinity receptors coupled to aggregation (spare receptors).(ABSTRACT TRUNCATED AT 250 WORDS)
Global analysis of myocardial isotonic shortening: comparison with isometric dynamics
Authors: Nwasokwa O. N. , Bodenheimer M. M.
Published: December 2017

Although potentially analytically useful, a global empirical model of the myocardial isotonic curve, L(t), has not been described. We propose the following relation: L(t) = C(t/A)B-1e-(t/A)B, where A, B, and C are global parameters, L is length, and t is time. We evaluated this model in nine in situ canine papillary muscles studied with a servo-system to produce isotonic twitches at different isotonic forces (F). For each twitch, the parameters were determined by nonlinear curve fitting. The model fit the observed curves of L(t) closely, with the coefficient of determination being 0.995 +/- 0.002. C changed with F, but A and B varied little with F, averaging 0.262 +/- 0.021 s and 2.76 +/- 0.17, respectively. Our predictions that A reflects chronotropic, B reflects lusitropic, and C reflects heterotonic (different afterloads) and inotropic states were supported. Comparison done in five muscles showed that A was the same but B was higher for isotonic than for isometric twitches: 0.270 +/- 0.020 vs. 0.264 +/- 0.038 s (P = not significant) for A and 2.79 +/- 0.18 vs. 2.39 +/- 0.05 (P less than 0.008) for B. Dobutamine increased A but not B in isotonic twitches. Thus shortening is lusitropic but leaves no lusitropic reserve to be mobilized by dobutamine. The relation L(t) = C(t/A)B-1e-(t/A)B provides a framework that undergirds global analysis of myocardial shortening and enables comparison with isometric dynamics.
Dependence of cerebral energy phosphate and evoked potential recovery on end-ischemic pH
Authors: Hurn P. D. , Koehler R. C. , Norris S. E. , Blizzard K. K. , Traystman R. J.
Published: December 2017

We determined whether the rate of metabolic recovery and electrophysiological deficit after incomplete cerebral ischemia is related to intracellular pH (pHi) achieved at the end of ischemia in a dose-dependent manner. End-ischemic pHi was varied by employing two ischemic durations, 12 and 30 min, and by setting preischemic plasma glucose to approximately 80 or 400 mg/dl. Incomplete global ischemia was produced in anesthetized dogs by transient intracranial hypertension followed by 4 h of reperfusion, and pHi, ATP, and phosphocreatine (PCr) were measured with 31P magnetic resonance spectroscopy. Cerebral blood flow was reduced to approximately 6 ml.min-1.100 g-1 during ischemia. End-ischemic pHi was greater than 5.7 in all animals from various treatment groups except for four of seven dogs treated with 30-min hyperglycemic ischemia. When end-ischemic pHi remained greater than 5.7, there was nearly complete recovery of ATP, PCr, pHi, intracellular bicarbonate concentration [( HCO3-]i), and O2 consumption. Partial recovery of somatosensory-evoked potentials (SEP) occurred in most of these animals. In the 30-min hyperglycemic animals in which pHi fell below 5.5, ATP, PCr, and O2 consumption recovered by only one-half over 60 min of reperfusion and then declined to near-zero levels without SEP recovery. In addition, pHi remained less than 6.0, and [HCO3-]i remained less than 2 mM throughout reperfusion. We conclude that there is an apparent in vivo pHi threshold of approximately 5.5-5.7 during incomplete cerebral ischemia that is associated with an inability to significantly restore pHi and [HCO3-]i and with secondary deterioration of high-energy phosphate levels.
Methylene blue prevents hypoxic pulmonary vasoconstriction in cats
Authors: Hyman A. L. , Lippton H. L. , Kadowitz P. J.
Published: December 2017

The influence of methylene blue, an inhibitor of soluble guanylate cyclase, on responses to ventilatory and precapillary hypoxia was investigated in the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. Because methylene blue increased vascular tone, responses to hypoxia were compared when lobar arterial pressure was raised to similar levels with U 46619 and with methylene blue. When lobar arterial pressure was raised with U 46619, ventilation with 7.5% O2 increased lobar arterial pressure significantly. Infusion of methylene blue in concentrations that raised lobar arterial pressure to a value similar to that attained with U 46619 prevented the pressor response to hypoxia, and a significant depressor response was unmasked. The depressor response to hypoxia in the methylene blue-treated animal was not altered by meclofenamate but was blocked by propranolol. A reduction in lobar arterial perfusate PO2 induces an increase in pulmonary vascular resistance in the cat, and this response was prevented by methylene blue. During methylene blue infusion, the vasodilator response to acetylcholine was reduced, whereas the response to isoproterenol was not altered. Although the response to hypoxia was prevented, the pressor response to prostaglandin F2 alpha was not changed. The response to ventilatory hypoxia was enhanced by propranolol or ICI 118551, suggesting that the response is modulated by circulating catecholamines that are probably of adrenal origin. The effects of methylene blue on vascular tone and responses to hypoxia and acetylcholine were reversible, and responses returned to control value after the infusion was terminated.(ABSTRACT TRUNCATED AT 250 WORDS)
Coronary vascular smooth muscle function in E. coli endotoxemia in dogs
Authors: Parker J. L. , Keller R. S. , DeFily D. V. , Laughlin M. H. , Novotny M. J. , Adams H. R.
Published: December 2017

The purpose of this study was to determine whether intrinsic contraction-relaxation properties of coronary arteries are altered during acute gram-negative endotoxemia. Coronary vascular smooth muscle (VSM) was evaluated in vitro using large and small left circumflex coronary ring preparations isolated from dogs 4 h after administration of either saline (control; C) or 1.5 mg/kg Escherichia coli endotoxin (ET). ET dogs exhibited marked systemic hypotension and cardiovascular depression throughout the 4-h in vivo phase of the study accompanied by reduction in total left ventricular myocardial blood flow. Isolated coronary vessels were stretched to the apex of the length-contractile tension curve; no differences were observed in length-active or length-passive tension (vessel compliance) relationships between C and ET vessels. Isometric contractions produced by K+ and prostaglandin F2 alpha (PGF2 alpha) were similar in C and ET coronary arteries. VSM relaxant responses to nitroprusside (NP; 10(-10) to 10(-4) M) were also similar in C and ET vessels. In contrast to the apparent lack of effect of ET on directly acting VSM agents, relaxation responses to the endothelial-dependent vasodilator acetylcholine (ACh) were significantly less in ET vessels. Impaired vasodilator response to ACh was not improved by in vivo treatment with the combination antioxidant therapy of allopurinol, superoxide dismutase, and catalase. We conclude that both depolarization (K+) and receptor (PGF2 alpha)-mediated contractile mechanisms, as well as basal cGMP (NP)-mediated vasodilator mechanisms, remained functional in coronary vasculature during acute endotoxemia. Inhibition of ACh-mediated relaxation in ET vessels suggests altered endothelial-dependent vasodilation in coronary arteries during endotoxemia, but this change did not seem to be associated causally with oxygen free radicals.
Power spectral analysis of blood pressure variability in traumatic quadriplegic humans
Authors: Inoue K. , Miyake S. , Kumashiro M. , Ogata H. , Ueta T. , Akatsu T.
Published: December 2017

A study was performed on seven traumatic neurologically complete quadriplegic (QP) males and seven age-matched healthy males (control) while they were at rest in the supine position in a climatic chamber (temperature 30 degrees C, relative humidity 60%). Arterial blood pressure waveforms were measured by a continuous noninvasive blood pressure-monitoring system based on arterial tonometry. Furthermore, the spontaneous beat-to-beat systolic blood pressure (SBP) variabilities of subjects were investigated by means of autoregressive power spectral analysis. As shown by earlier studies with an invasive (intra-arterial) blood pressure-monitoring system, in the control group there were two major spectral components: a high-frequency (HF) component [center frequency 0.27 +/- 0.02 (SE) Hz eq, power 0.9 +/- 0.2 mmHg2] and a low-frequency (LF) component (0.10 +/- 0.01 Hz eq, 5.2 +/- 1.4 mmHg2). On the contrary, in the QP group only the HF component was observed (0.28 +/- 0.03 Hz eq, 3.2 +/- 1.4 mmHg2). The results suggest that 1) in the QP subject the disappearance of the LF component in the SBP variability (i.e., the Mayer waves in humans) is presumably caused by the interruption of the spinal pathways linking supraspinal cardiovascular centers with the peripheral sympathetic outflow and 2) the cervical spinal sympathetic pathways may be instrumental in the genesis of the Mayer waves in humans.
Decreased transient outward K+ current in ventricular myocytes from acromegalic rats
Authors: Xu X. P. , Best P. M.
Published: December 2017

Cardiac hypertrophy and heart failure are common to acromegalic patients who have abnormally high serum growth hormone (GH). While the function of cardiac muscle is clearly affected by chronically elevated GH, the electrical activity of myocytes from hearts with GH-dependent hypertrophy has not been studied. We used adult, female Wistar-Furth rats with induced GH-secreting tumors to study the effect of excessive GH on ion channels of cardiac myocytes. GH-secreting tumors were induced by subcutaneous inoculation of GH3 cells. Eight weeks after inoculation, the rats had doubled their body weight and heart size compared with age-matched controls. There were no differences in either action potential amplitude or resting potential of right ventricular myocytes from control and tumor-bearing rats. However, action potential duration increased significantly in tumor-bearing rats; the time to 50% repolarization was 23 +/- 14 ms (n = 10) compared with 6.6 +/- 1.5 ms (n = 14) in controls. The prolongation of the action potential was mainly due to a decrease in density of a transient outward current (It,o) carried by K+. The normalized conductance for It,o decreased from 0.53 +/- 0.10 nS/pF (n = 25) in controls to 0.33 +/- 0.09 nS/pF (n = 26) in tumor-bearing rats. The decrease in It,o) and increase in heart weight occurred with a similar time course. The increased action potential duration prolongs Ca2+ influx through L-type Ca2+ channels in the tumor-bearing animals; this may be important in cardiovascular adaptation.
Analysis of pulmonary and systemic vascular responses to cromakalim, an activator of K+ATP channels
Authors: Minkes R. K. , Kvamme P. , Higuera T. R. , Nossaman B. D. , Kadowitz P. J.
Published: December 2017

Cardiovascular and pulmonary responses to cromakalim, a member of a novel class of antihypertensive agents that open ATP-sensitive K+ (K+ATP) channels, were investigated in the anesthetized cat. Intravenous injections of cromakalim in doses of 30-300 micrograms/kg decreased arterial pressure (AP), pulmonary arterial pressure (PAP), and increased cardiac output (CO), while producing small changes in right and left atrial pressures. Pulmonary and systemic vascular resistances were decreased and vasodilator responses to cromakalim were blocked by glybenclamide, a K+ATP channel-blocking agent. The low dose of cromakalim caused a reflex increase in heart rate (HR) and right ventricular contractile force (RVCF), whereas the high dose decreased HR and RVCF. Under constant-flow conditions the K+ATP channel opener caused dose-dependent decreases in hindquarters perfusion pressure, and when tone was elevated in the pulmonary vascular bed, dose-dependent decreases in pulmonary lobar arterial perfusion pressure. Hindquarters and pulmonary lobar vasodilator responses to cromakalim were inhibited in a specific manner by glybenclamide. The present data show that cromakalim has significant vasodilator activity in both the systemic and pulmonary vascular beds and suggest that responses to this agent result from activation of glybenclamide-sensitive K+ATP channels. These data show that cromakalim can cause substantial decreases in systemic and pulmonary vascular resistance in a dose that has little effect on RVCF.
Right and left atrial diameters during incremental atrial pacing in pigs
Authors: Leistad E. , Christensen G. , Ilebekk A.
Published: December 2017

The relationship between right and left atrial diameters and heart rate was examined in 14 open-chest barbiturate-anesthetized pigs by an ultrasonic technique. The maximal atrial diameter was read at the top of the v wave, which decreased in both atria when heart rate was increased from 124 (118-130) to 159 (156-160) (median and 95% confidence interval) beats/min. Right and left atrial maximal diameter fell significantly from 25.7 (23.6-32.6) to 24.9 (22.9-29.5) mm and from 30.8 (25.1-37.2) to 29.8 (23.4-36.3) mm, respectively, when heart rate was increased from 124 to 180 (177-182) beats/min. At higher pacing frequencies, both right and left atrial maximal diameter progressively increased, and at 220 (216-221) beats/min the maximal diameter regained the values obtained at 124 beats/min. The minimal atrial diameter, which was read at the end of the a wave, remained unchanged at heart rates below 180 beats/min but rose significantly at higher rates. Our findings indicate progressively reduced atrial filling with increasing heart rate and hampered atrial emptying and atrial distension at the highest heart rates.
Adenosine deaminase and adenosine attenuate ventricular arrhythmias caused by norepinephrine
Authors: Friedrichs G. S. , Merrill G. F.
Published: December 2017

Twenty-five beagles weighing 9.1 +/- 0.4 kg were used to investigate the arrhythmogenic effects of divided doses of intracoronary norepinephrine (50-200 ng.kg-1.min-1) in the absence and the presence of adenosine deaminase (5 U.kg-1.min-1). A dose of norepinephrine (100 ng.kg-1.min-1) that caused 66 +/- 17% ectopy in the absence of adenosine deaminase caused only 16 +/- 14% ectopy (P less than 0.05) in the presence of the enzyme. Ventricular tachycardia caused by 200 ng.kg-1.min-1 norepinephrine was reduced from 1.2 +/- 0.3 to 0.1 +/- 0.1 bouts/10 cardiac cycles (P less than 0.05) by adenosine deaminase. In five additional dogs, intracoronary adenosine (0.11 mumol/min) terminated sustained norepinephrine-induced (200 ng.kg-1.min-1) ventricular tachycardia within 23 +/- 9 s (P less than 0.05). As long as the adenosine infusion was maintained, a normal sinus rhythm was observed. We conclude that both adenosine and adenosine deaminase significantly attenuate norepinephrine-induced ventricular arrhythmias. A common element beyond the deamination of adenosine, quite possibly ammonia, appears to account for these results.
Acid-base status affects gas exchange in canine oleic acid pulmonary edema
Authors: Brimioulle S. , Vachiery J. L. , Lejeune P. , Leeman M. , Melot C. , Naeije R.
Published: December 2017

The effects of acidosis and alkalosis on pulmonary gas exchange were studied in 32 pentobarbital sodium-anesthetized intact dogs after induction of oleic acid (0.06 ml/kg) pulmonary edema. Gas exchange was assessed at constant ventilation and constant cardiac output, by venous admixture calculations and by intrapulmonary shunt measurements using the sulfur hexafluoride (SF6) method. Metabolic acidosis (pH 7.20) and alkalosis (pH 7.60) were induced with HCl and Carbicarb (isosmolar Na2CO3 and NaHCO3), respectively. Hypercapnia was induced by adding inspiratory CO2, whereas pH was allowed to change (respiratory acidosis, pH 7.20) or maintained constant (isolated hypercapnia). Mean intrapulmonary shunt and pulmonary arterial minus wedge pressure difference, respectively, changed from 44 to 33% (P less than 0.05) and from 9 to 10 mmHg (P greater than 0.05) in metabolic acidosis, from 44 to 62% (P less than 0.001) and from 12 to 8 mmHg (P less than 0.01) in metabolic alkalosis, from 40 to 42% (P greater than 0.05) and from 13 to 16 mmHg (P less than 0.05) in respiratory acidosis, from 42 to 52% (P less than 0.05) and from 8 to 12 mmHg (P less than 0.01) in isolated hypercapnia. These results indicate that acidosis, alkalosis, and hypercapnia markedly influence pulmonary gas exchange and/or pulmonary hemodynamics in dogs with oleic acid pulmonary edema.
Cardiovascular effects of endothelin in trout
Authors: Olson K. R. , Duff D. W. , Farrell A. P. , Keen J. , Kellogg M. D. , Kullman D. , Villa J.
Published: December 2017

The cardiovascular effects of endothelin-1 (ET-1) in trout were examined in unanesthetized fish, perfused tissues, and isolated vascular rings. In vivo, a bolus of 500 ng/kg body wt ET-1 transiently lowered arterial (postgill) blood pressure (BP) by nearly 30%; 1,500 ng/kg body wt produced a triphasic, pressor-depressor-pressor, response. Continuous infusion of 0.1, 1, 10, and 30 ng.kg-1.min-1 progressively lowered BP but did not affect heart rate (HR), urine flow, or electrolyte excretion. In the in situ perfused heart ET-1 (10(-11) to 10(-8) M) had no effect on HR or power output. ET-1 produced dose-dependent increases in vascular resistance in the perfused gill, renal-skeletal muscle, and splanchnic circulations, and increased tension, independent of endothelium, in vascular rings from celiacomesenteric (CA) and coronary arteries and anterior cardinal veins (CV). Ventral aortas were refractory to ET-1. In vitro, ET-1 effects were slow in onset and long lasting. External calcium was required for maximal ET-1 responses in gill and CA. ET-1 effects on CA but not CV were partially inhibited by calcium channel blockers, diltiazem, and D 600, and by the guanylate cyclase activators, atrial natriuretic factor, and sodium nitroprusside. [3H]water flux across the perfused gill was stimulated by ET-1 through what appeared to be a vascular-independent mechanism. These experiments show that the trout vasculature is exquisitely sensitive to ET-1, and they suggest that the physiological expression of this peptide has been highly conserved during the course of vertebrate evolution.
Heterogeneity in conducted arteriolar vasomotor response is agonist dependent
Authors: Delashaw J. B. , Duling B. R.
Published: December 2017

Microiontophoresis of acetylcholine onto cheek pouch arterioles of the pentobarbital-anesthetized hamster results in both a local response at the pipette tip and a conducted dilator response. The conducted response is not dependent on blood flow, and its magnitude decays with distance from the site of stimulation. In an attempt to define the mechanism responsible for activation of arteriolar conduction, vasoactive agonists directed toward different vascular wall cell types, receptor types, and second messengers were applied to arterioles by pressure-pulse microejection. As expected, microapplication caused a consistent arteriolar response at the site of application with each of the agonists tested (local response). However, a high degree of variability was observed among agonists in their ability to produce conducted responses. Acetylcholine, muscarine, and phenylephrine, invariably induced both local and conducted responses. In contrast, bradykinin, substance P, papaverine, isoproterenol, and adenosine, though consistently inducing local responses, displayed a highly variable ability to induce the conducted responses. When conduction was observed, the arteriolar response was similar regardless of the agonist used to induce the response. Microejection of sodium nitroprusside or arginine vasopressin produced local arteriolar responses with no evidence of a conducted response regardless of the dose. These studies reveal previously undetected heterogeneity among microvessel responses and may reflect variations in the coupling mechanisms linking the local vasomotor response to the conducted response.
Repolarization differences between guinea pig atrial endocardium and epicardium: evidence for a role of Ito
Authors: Wang Z. G. , Fermini B. , Nattel S.
Published: December 2017

It has long been known that ventricular epicardial action potential duration (APD) is shorter than endocardial, and recent evidence suggests that a larger transient outward current (Ito) in epicardium is responsible for the difference. To evaluate possible corresponding regional variations in atrial tissue, we studied guinea pig atrial epicardial and endocardial action potentials using standard microelectrode techniques. Epicardial APD was consistently shorter than endocardial, but the difference was greatly diminished by rapid pacing or early premature activation, situations in which Ito availability should be limited. 4-Aminopyridine (4-AP), at concentrations (0.5 mM) producing specific Ito blockade, increased APD significantly in atrial epicardium without affecting endocardium. The effect of 4-AP on APD was most marked at slow rates, at which Ito would be greatest, and was negligible at rapid rates or during premature activation, during which Ito would be largely inactivated. At larger concentrations (5 mM) 4-AP caused an equalization of epicardial and endocardial APD. The equimolar substitution of strontium for calcium did not affect APD at slow rates and increased APD (particularly in endocardium) at rapid rates, suggesting that the Ito underlying endocardial-epicardial differences was unlikely to be calcium dependent. We conclude that epicardial-endocardial differences in APD, well documented in ventricular tissue, can also occur in atrial tissue and that the underlying ionic mechanisms appear to be similar.
Intravenous injection of hypertonic NaCl solution stimulates pulmonary C-fibers in dogs
Authors: Pisarri T. E. , Jonzon A. , Coleridge H. M. , Coleridge J. C.
Published: December 2017

Intravenous injection of hypertonic NaCl solution evokes reflex bradycardia and hypotension, effects thought to result from stimulation of afferent vagal endings in the lungs. To identify the afferents responsible for these effects, we recorded vagal impulses arising from endings in the lungs and lower airways of anesthetized dogs and examined the response to injection of hypertonic solutions into the pulmonary circulation. Injection of 4,800 mmol/l NaCl solution (1 ml/kg) stimulated 39 of 49 pulmonary C-fibers, their impulse frequency increasing 35-fold. Stimulation was concentration dependent, the minimum effective concentration being between 1,200 and 4,800 mmol/l. Rapidly adapting receptors were also stimulated in a concentration-dependent manner, 35 of 41 receptors being stimulated by 4,800 mmol/l NaCl solution, firing increasing fivefold. Bronchial C-fibers were not stimulated by injection into the pulmonary circulation but were by injection into the bronchial artery. Hypertonic urea solutions had qualitatively similar but smaller effects on pulmonary C-fibers and rapidly adapting receptors. The results suggest that the reflex effects of intravenous injection of hypertonic solutions result principally from stimulation of pulmonary C-fibers.
Loss of intermediate-sized coronary arteries and capillary proliferation after left ventricular failure in rats
Authors: Anversa P. , Capasso J. M.
Published: December 2017

To determine the adaptation of coronary vasculature and microvasculature to cardiac failure, renal hypertension was produced in rats, and the animals were killed 8 mo later when severe impairment in left ventricular function was present. By use of a new morphometric approach, it could be demonstrated that length densities of arteries from 6 to 20 microns in luminal diameter decreased by 23 and 26% in the midmyocardium and endomyocardium, respectively, whereas arteries ranging from 21 to 40 microns were reduced by 59, 55, and 46% in the outer, middle, and inner layers, respectively, of the left ventricular wall. In contrast, capillary density increased by 29 and 38% in the epimyocardium and endomyocardium, respectively. Capillary proliferation resulted in a 15% decrease in average diffusion distance for oxygen to the myocyte compartment of the tissue. Despite these opposite effects that may tend to compensate each other, the volume percent of collagen in the wall augmented by 106%. In conclusion, differences exist in the response of the coronary vascular tree to long-term renal hypertension that may impair coronary resistance and flow without affecting the capillary network and the oxygenation potential of muscle cells.
Mechanical characteristics and active tension generation in rat intestinal arterioles
Authors: Lash J. M. , Bohlen H. G. , Waite L.
Published: December 2017

The contributions of active and passive wall tension to regulation of arteriolar diameters were determined for large (1A), intermediate (2A), and small (3A) arterioles in the small intestine of the anesthetized rat. Active tension (Ta) contributed greater than 85% of total wall force at rest in 2A and 3A and 75-80% of total force in 1A. Ta was approximately 90% of peak active tension (Ta,peak) for large through small arterioles, even though absolute Ta varied by fourfold. A linear relationship between microvascular pressure and Ta was observed for decreases in pressure in all arterioles. Ta remained nearly constant for pressure increases of 40% in 2A and 3A but was increased in 1A. Because of the plateau of the circumference-Ta relationship near Ta,peak, superfusion of progressively increasing concentrations of norepinephrine or adenosine resulted in maintenance of the close Ta-Ta,peak relationship unless the vessel diameter changed greater than 25%. These results indicate that, while arteriolar diameters vary substantially, near-peak Ta is generated for a variety of physiological conditions.
Calcium mobilization and glycoprotein IIb-IIIa complex ligands in epinephrine-stimulated platelets
Authors: Ware J. A. , Decenzo M. T. , Smith M. , Saitoh M.
Published: December 2017

In the presence of extracellular Ca2+, epinephrine induces a rise in cytoplasmic Ca2+ ([Ca2+]i) that is associated with fibrinogen binding to the platelet surface, platelet aggregation, and enhancement of the thrombin-stimulated [Ca2+]i rise and protein phosphorylation. Whether the [Ca2+]i rise induced by epinephrine results from Ca2+ entry associated with fibrinogen binding to its receptor on the platelet surface, the glycoprotein (gp) IIb-IIIa complex, is unknown. To determine the importance of the occupancy of the gp IIb-IIIa receptor on platelet function after epinephrine administration, we studied the effects of two monoclonal antibodies (M-148 and 7E3) and two synthetic peptide analogues to fibrinogen (synthetic tetrapeptides Arg-Gly-Asp-Ser (RGDS) and dodecapeptide His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val [gamma-(400-411)]), all of which bind to gp IIb-IIIa and inhibit fibrinogen binding and platelet aggregation on the epinephrine-induced rise in [Ca2+]i and enhancement of thrombin's phosphorylation of the 47-kDa substrate of protein kinase C (p47). None of the gp IIb-IIIa ligands significantly enhanced or inhibited the epinephrine-induced [Ca2+]i rise or its augmentation of p47 phosphorylation after thrombin administration; however, the synergistic [Ca2+]i rise that follows addition of both epinephrine and thrombin was reduced by both antibodies and both peptides. Thus ligand binding of gp IIb-IIIa does not influence the epinephrine-induced [Ca2+]i rise or its promotion of protein kinase C activation by thrombin; these events can be dissociated from the synergistic [Ca2+]i rise.
Effects of beta-hydroxybutyrate on oxidative metabolism and phosphorylation potential in canine heart in vivo
Authors: Kim D. K. , Heineman F. W. , Balaban R. S.
Published: December 2017

beta-Hydroxy-butyrate (HBA) is an effective substrate for mitochondrial respiration (MVO2) in the heart. Myocardial HBA oxidation is associated with high mitochondrial NADH and an inhibition of glycolytic flux. The purpose of this study was to investigate if the infusion of HBA in vivo could modify the coupling mechanisms between myocardial MVO2 and work in the presence and absence of epinephrine. The extraction of several oxidized metabolites, O2, and HBA was measured during the infusion of HBA as well as the high-energy phosphate metabolites using 31P-nuclear magnetic resonance spectroscopy. HBA infusion did not affect the MVO2 or function of the heart with or without epinephrine infusion. However, HBA increased the phosphorylation potential by decreasing inorganic phosphate and the calculated free ADP concentration under both conditions. This is consistent with HBA increasing the mitochondrial NADH, which results in an increase in the phosphorylation potential without modifying function. These data demonstrate that substrates, specifically HBA, can modulate the cardiac phosphorylation potential in vivo. The most likely mechanism for this effect is through the mitochondrial NADH concentration.
Vascular viscoelasticity of perfused rat hindquarters
Authors: Chihara E. , Morimoto T. , Shigemi K. , Natsuyama T. , Hashimoto S.
Published: December 2017

To determine viscoelastic features of the rat hindquarters vasculature, we measured pressure-volume curves. Male Wistar rats were transected at the lumbar level, and the perfused hindquarters were oxygenated with a hollow fiber artificial lung. The blood volume was measured by counting 51Cr-labeled red cells led to a gamma counter through an extracorporeal circuit at a constant rate. With continuous monitoring of the venous pressure and circulating blood volume, saline was infused into the circuit from a venous branch for 5 min [1.2 +/- 0.3% (SD) of tissue weight] followed by a 10-min recovery phase. In the recovery phase, the venous pressure promptly declined to the preinfusion level, whereas the circulating blood volume decreased more slowly. This implied vascular stress relaxation of the hindquarters. Maxwell's viscoelastic model, consisting of a spring component and a viscous component, was applied to analyze the venous pressure-volume diagram. With a curve-fitting method, the calculated vascular compliance and relaxation time (a time constant of stress relaxation) were 1.31 +/- 0.14 ml.mmHg-1.kg-1 and 15.7 +/- 4.0 min (means +/- SE), respectively. The value of compliance of the hindquarters was smaller than those of visceral organs reported. In addition, the value for relaxation time suggests that the viscous response of the vasculature simultaneously overlaps change in blood volume due to extravascular fluid shift during the postinfusion period.
Neutrophil elastase and oxygen radicals: synergism in lung injury after hindlimb ischemia
Authors: Welbourn C. R. , Goldman G. , Paterson I. S. , Valeri C. R. , Shepro D. , Hechtman H. B.
Published: December 2017

Hindlimb ischemia and reperfusion lead to lung injury dependent on activated polymorphonuclear neutrophils (PMN) adherence. This study tests whether elastase and oxygen radicals participate in PMN-induced injury once they have become sequestered in lungs. Anesthetized rats treated with saline (n = 9) or the specific elastase inhibitor methoxysuccinyl-L-Ala-L-Ala-L-Pro-L-Val-chloromethylketone (MAAPV, n = 6) underwent 4 h of bilateral hindlimb tourniquet ischemia followed by 4 h of reperfusion. At this time, in saline-treated rats, PMN were sequestered in lungs as assayed by myeloperoxidase activity [(MPO) 51 +/- 5 U/g tissue], higher than MPO in saline-treated sham rats (n = 9; 18 +/- 3 U/g MPO; P less than 0.01); bronchoalveolar lavage (BAL) fluid leukotriene (LT) B4 levels increased to 594 +/- 46 relative to 200 +/- 38 pg/ml in shams (P less than 0.01); increased permeability was documented by BAL fluid protein content of 599 +/- 91 compared with 214 +/- 35 micrograms/ml in sham animals (P less than 0.01); and edema was shown by increase in lung wet-to-dry weight ratio of 4.77 +/- 0.14 relative to 4.00 +/- 0.09 in sham rats (P less than 0.01). In MAAPV-treated animals, lung neutrophil sequestration (62 +/- 9 U/g MPO) and rise of LTB4 in BAL fluid (780 +/- 244 pg/ml) were not affected, but both BAL fluid protein (335 +/- 32 micrograms/ml) and lung wet-to-dry weight ratio (4.21 +/- 0.17) were reduced (both P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Heart rate perturbation in chick embryos: a comparison of two methods
Authors: Cuneo B. , Hughes S. , Benson D. W.
Published: December 2017

This report compares the effects of two methods of heart rate (HR) perturbation on stroke volume and dorsal aortic flow in the Hamburger-Hamilton stage 24 chick embryo. The sinus venosus was paced at intrinsic HR and at 150, 125, 75, and 50% of intrinsic HR (n = 23). Alternatively, a 1-mm steel probe heated to increase and cooled to decrease HR was applied to the sinus venosus (n = 15). All studies were performed in ovo at 37–38 degrees C. Aortic flow (mm3/S) and stroke volume (mm3/beat) were calculated from aortic velocity, aortic cross-sectional area, and HR. Atrioventricular (AV) inflow velocities were measured during pacing (n = 10) or probe application (n = 11) technique. Dorsal aortic flow was maximum at intrinsic HR and decreased at both increased and decreased HR. Stroke volume decreased proportionally to HR during rate increase. At decreased HR, when AV synchrony was disrupted (pacing), stroke volume was unchanged from intrinsic values. However, when AV synchrony was maintained at decreased HR (cold probe), the embryonic ventricle significantly increased stroke volume.
Hypotension during vasopressin receptor blockade: role of V2 receptors and sympathetic nervous system
Authors: Brooks V. L. , Hatton D. C.
Published: December 2017

This study investigated possible mechanisms for the hypotension produced by nitroprusside infusion in conscious dogs pretreated with a V1 vasopressin antagonist. The hypothesis that an action of vasopressin at V2-like receptors contributes to the hypotension was tested by comparing the effects of a V1 antagonist to the effects of a combined V1/V2 antagonist. Nitroprusside infusion produced dose-dependent decreases in arterial and atrial pressures. Larger decreases in pressures were produced in animals pretreated with either antagonist; however, the decreases in V1/V2-blocked dogs were not less than the decreases in V1-blocked dogs. These data suggest that V2-like actions of vasopressin do not contribute to the hypotensive effects of V1 blockade. A second hypothesis was that the greater hypotension was due to activation of a cardiac reflex to cause withdrawal of sympathetic tone, a decrease in peripheral resistance, and adrenal activation. Measurement of cardiac output revealed that the larger decreases in arterial pressure were due to larger decreases in total peripheral resistance. The hypotension was also associated with decreases in heart rate, unchanging plasma norepinephrine concentration, and increases in epinephrine concentration. These data are consistent with the hypothesis that the fall in pressure observed in dogs pretreated with a V1 antagonist is secondary to a decrease in peripheral resistance that is due at least in part to withdrawal of sympathetic tone.
Reactive oxygen metabolites inhibit spontaneous lymphatic contractions
Authors: Zawieja D. C. , Greiner S. T. , Davis K. L. , Hinds W. M. , Granger H. J.
Published: December 2017

The effects of oxygen-derived free radicals on the contractile activity of the mesenteric collecting lymphatics were evaluated in the anesthetized rat. Lymphatic contractions were monitored before, during and after the application of oxyradicals. Contraction frequency (F), stroke volume (SV), ejection fraction (EF), contraction propagation (PC), and lymph pump flow (LPF) were determined from the lymphatic diameter tracings. Oxyradicals were generated using hypoxanthine and xanthine oxidase. Exposure to oxyradicals inhibited the lymphatic pumping mechanism: 1) F fell from 15.5 +/- 0.8 to 0.8 +/- 0.7 beats/min; 2) EF went from 0.44 +/- 0.02 to 0.08 +/- 0.04; 3) PC dropped from 92 +/- 2 to 56 +/- 8%; and 4) LPF fell precipitously from 41.0 +/- 5.2 to 0.7 +/- 0.4 nl/min. The effects of the oxyradicals were attenuated by superoxide dismutase, implicating superoxide anion as one of the predominant causative agents. We conclude that oxyradicals significantly inhibit the lymph pump and that this inhibition could be a factor contributing to the formation of interstitial edema during inflammation.
Arterial vasodilation and cardiovascular structural changes in normotensive rats
Authors: Tsoporis J. , Fields N. , Lee R. M. , Leenen F. H.
Published: December 2017

In normotensive rats, the arterial vasodilator minoxidil causes right ventricular hypertrophy (RVH) and eccentric left ventricular hypertrophy (LVH). To assess whether this trophic effect of minoxidil extends to the vasculature and to examine possible mechanisms involved, alterations in cardiac and arterial (superior, large and small mesenteric arteries, carotid and basilar arteries) structure were evaluated in relation to changes in indexes of cardiac volume load and cardiac and arterial sympathetic activity during long-term (35 and 70 days) treatment of normotensive rats with minoxidil alone or in combination with the diuretic hydrochlorothiazide (HCTZ). Minoxidil alone increased LV and RV weights, LV internal diameter, and medial area of the superior mesenteric artery but did not affect any of the other arteries evaluated. When combined with HCTZ, long-term minoxidil caused concentric LVH rather than eccentric LVH and no longer increased the medial area of the superior mesenteric artery. Neither treatment had any persistent effect on blood pressure, heart rate, or plasma catecholamines. However, minoxidil significantly increased cardiac and arterial (superior and large mesenteric artery) norepinephrine turnover rates, cardiac filling pressures, and plasma and blood volumes. When combined with HCTZ, short-term (1 wk) minoxidil still increased cardiac filling pressures. However, intravascular volume expansion during chronic treatment was significantly attenuated. These results suggest that chronic cardiac volume load appears to determine the type of cardiac hypertrophy induced by a nonhemodynamic mechanism (possibly cardiac sympathetic activity) activated by minoxidil. Intravascular volume expansion or increased arterial flow appears to be responsible for medial hypertrophy of the superior mesenteric artery, but absence of a trophic response in other arteries suggests that another, local mechanism contributes.