bluuebunny/crossref_metadata_2025 huggingface dataset:
Time course of hemodynamic changes in rats with healed severe myocardial infarction
Authors: DeFelice A. , Frering R. , Horan P.
Published: December 2017

Male rats were monitored for 8 mo after severe myocardial infarction (MI) to chronicle hemodynamic and left ventricular (LV) functional changes. Blood pressure (BP), heart rate (HR), cardiac output index (CO), regional blood flow, and systemic vascular resistance (SVR) were measured with catheters and radiolabeled microspheres at 4, 7, 10, 20, and 35 wk after coronary artery ligation (n = 10–16/group) or sham operation (control; n = 9–14/group). At 4 wk, 43 +/- 1% of the LV circumference was scarred, peak LV BP, LV dP/dtmax, mean BP, SVR, and HR were 11–38% less than control (P less than 0.05), and LV end-diastolic pressure (LVEDP) was increased by 313% (P less than 0.05). Mean BP, LVEDP, LVBP, and LV dP/dtmax did not further deviate after 4 wk. However, CO and SVR changed progressively and were 67 and 33%, respectively, of control by 35 wk (P less than 0.05) when blood flow to stomach, small intestine, and kidney was 55, 38, and 27% of control. Lung and heart weights were significantly increased by 148 and 22% at 4 wk, and remained elevated, and lung dry weight-to-wet weight ratio was reduced at 7 and 10 wk. Thus the trajectory of rats with healed severe MI reflects progressive cardiac decompensation, cardiac output redistribution, and terminal heart failure.
Cardiovascular effects of angiotensin-(1-7) injected into the dorsal medulla of rats
Authors: Campagnole-Santos M. J. , Diz D. I. , Santos R. A. , Khosla M. C. , Brosnihan K. B. , Ferrario C. M.
Published: December 2017

The amino terminal angiotensin heptapeptide, Asp-Arg-Val-Tyr-Ile-His-Pro [ANG-(1–7)], is the major product formed during incubation of 125I-labeled ANG I or 125I-labeled ANG II with homogenates obtained from canine dorsomedial medulla oblongata. To determine whether ANG-(1–7) has central-mediated cardiovascular effects, this heptapeptide was microinjected into the dorsal medulla of chloralose-urethan-anesthetized rats. Unilateral injections of ANG-(1-7) into the medial nucleus tractus solitarii caused depressor and bradycardic effects at doses between 0.1 and 12.5 ng. Similar hypotensive responses accompanied with bradycardia were produced by injections of ANG-(1–7) into the dorsal motor nucleus of the vagus. In both nuclei, the monophasic depressor responses elicited by ANG-(1–7) were qualitatively similar to those found with injections of ANG II. Biphasic depressor-pressor responses of variable magnitude were produced by the injection of either angiotensin peptide at a high dose (250 ng). Because ANG-(1–7) has no direct vascular or dipsogenic effects, our findings suggest important differences in the receptor requirements for vascular and neural tissue of the dorsal medulla. Moreover, the data support the concept of tissue specific formation and action of angiotensin peptides in the brain.
Effect of increased pressure on ventricular growth in stage 21 chick embryos
Authors: Clark E. B. , Hu N. , Frommelt P. , Vandekieft G. K. , Dummett J. L. , Tomanek R. J.
Published: December 2017

We studied the effect of increased ventricular pressure on heart growth in the stage 21 (3.5-day) chick embryo. Ventricular pressure was increased by constricting the conotruncus with a loop of 10-0 nylon tied in an overhand knot. The embryos were reincubated, and physiology and cellular morphology were evaluated at successive stages of development, stages 21, 24, 27, and 29. Ventricular pressure was measured with a servo-null pressure system, and cardiac output was measured with a 20-MHz pulsed Doppler velocity meter. Ventricular and embryo dry weights were measured on an electronic microbalance, myocyte organelle composition was measured by a point counting technique, and cell growth response was measured by DNA and protein assay. The conotruncal loop increased ventricular pressure in experimental compared with control embryos, i.e., at stage 24, 2.88 +/- 0.13 vs. 1.96 +/- 0.05 (SE) mmHg (P less than 0.05), respectively, without affecting cardiac output. Ventricular dry weight increased in experimental vs. control embryos, i.e., at stage 24, 114 +/- 7 vs. 85 +/- 4 micrograms (P less than 0.05), respectively, whereas embryo weights were similar between the two groups. The difference in ventricular weights was due to myocyte hyperplasia, since organelle proportion of myofibrils and mitochondria, DNA-to-protein ratio, and myocyte area were similar in experimental voice control embryos. Thus the adjustment of myocardial mass to ventricular work occurs even during the earliest stages of embryonic development. Cardiac growth and morphogenesis are parallel but separable processes.
Vasopressin-induced pulmonary vasodilation in rats
Authors: Walker B. R. , Haynes J. , Wang H. L. , Voelkel N. F.
Published: December 2017

Experiments were performed to determine the pulmonary vascular responses to exogenous or endogenous arginine vasopressin (AVP) in rats. Both in vitro and in vivo approaches were used to examine the direct pulmonary vasoactive properties of AVP and how those properties affect pulmonary hemodynamics in the intact animal. In conscious, unrestrained rats, constant infusion of AVP (4.0 mU.kg-1.min-1 iv) resulted in a fall in mean pulmonary artery pressure (PAP), although systemic pressure was increased. Coincident with the fall in PAP were similar reductions in cardiac output and heart rate. Similarly, bolus administration of AVP reduced PAP, and this effect was augmented during hypoxia. Another series of experiments examined the effect of endogenous AVP released by arterial hypoxemia on pulmonary hemodynamics in conscious rats. Administration of a specific V1-vasopressinergic antagonist had no effect on the PAP response to hypoxia; however, systemic resistance tended to fall following V1-antagonism. To determine the vasoactive properties of AVP independent of these changes in blood flow, a series of experiments were performed on isolated, perfused rat lungs. Injection of 25, 200, or 2,000 mU of AVP into the circulation of the isolated lung was without effect under normoxic conditions. In contrast, 25 mU AVP elicited reproducible pulmonary vasodilation when injected during ongoing hypoxic pulmonary vasoconstriction. This vasodilatory response was unaffected by meclofenamate or by the platelet-activating factor receptor antagonist SRI 63-441, but was blocked by a specific V1-vasopressinergic antagonist. We conclude that although AVP exerts profound systemic vasoconstriction, the pulmonary circulation appears relatively unaffected by exogenous or endogenous AVP in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Platelets adhere to thrombin-treated endothelial cells in vitro
Authors: Kaplan J. E. , Moon D. G. , Weston L. K. , Minnear F. L. , Del Vecchio P. J. , Shepard J. M. , Fenton J. W.
Published: December 2017

Interaction of thrombin with vascular endothelial cells was investigated as a mechanism promoting platelet activation and adherence to endothelial monolayers. We found that pretreatment of endothelium with alpha-thrombin in the absence of platelets results in the attachment of platelets to endothelial cells after the removal of fluid-phase alpha-thrombin. This activity was eliminated by exposure of alpha-thrombin-pretreated endothelial cells to active site inhibitors of alpha-thrombin or by adding alpha-thrombin in the presence of excess diisopropyl fluorophosphate-inhibited thrombin, suggesting retention of active alpha-thrombin by a receptor-mediated mechanism. Morphological data and the results of [14C]serotonin release studies indicate that platelets are activated by alpha-thrombin-pretreated endothelium and that adherence represents aggregates of activated platelets as well as individual platelets. Adherence on alpha-thrombin-pretreated endothelium is dependent on divalent cations. Platelets also adhered to aortic segments pretreated with thrombin. The data of the current studies support the contention that alpha-thrombin can promote adherence of activated platelets to endothelial cells because of the binding and retention of alpha-thrombin to endothelial cells in a manner in which it remains active and available for platelet activation.
Resistance of endothelial cells to anoxia-reoxygenation in isolated guinea pig hearts
Authors: Buderus S. , Siegmund B. , Spahr R. , Krutzfeldt A. , Piper H. M.
Published: December 2017

The release of cytosolic enzymes from myocardial and endothelial cells in the anoxic-reoxygenated guinea pig heart was investigated. Isolated hearts were perfused with Tyrode solution in the Langendorff mode. Sixty-minute anoxic perfusion with or without glucose (5 mM) was followed by 15-min normoxic perfusion with glucose. The losses of purine-nucleoside phosphorylase (PNP) from endothelial cells and of lactate dehydrogenase (LDH) and creatine kinase (CK) from the mass of myocardial cells were determined. After 30-min anoxia, the release of LDH and CK but not of PNP increased. Reoxygenation after 60-min anoxia with glucose caused a partial recovery of tissue ATP but also an increase in leakage of LDH (11% of total in 15 min) and CK (10%) and a sudden rise in coronary resistance, indicating contracture development ("oxygen paradox"). PNP release remained low (0.5%). In hearts subjected to glucose-free anoxia, ATP levels did not rise during 15-min reoxygenation, contracture development was delayed, and the release of LDH and CK was diminished (3.1 and 2.7%, respectively). Leakage of PNP was again low (0.5%). The results indicate that cardiomyocytes are more severely injured by anoxia-reoxygenation than the coronary endothelium. The rapidly developing reoxygenation-induced injury of cardiomyocytes seems to be an energy-dependent phenomenon, since it was attenuated in hearts deprived of substrate in anoxia.
A dynamic analysis of cardiovascular regulation using sinusoidal acceleration in dogs
Authors: Randall D. C. , Marquis J. A. , Evans J. M. , Knapp C. F.
Published: December 2017

Control of cardiovascular function during time-dependent pooling of blood in the upper and lower body was studied in intact dogs (n = 5) and in dogs in which hearts had been surgically denervated (n = 5). The animal was positioned horizontally on a platform mounted on the arm of a centrifuge; rotation of the platform at one of nine rates with a period ranging from 3.3 min to 4 s exposed the subject to a sinusoidally varying force (+/- 2 g) that periodically translocated blood from the chest to the lower quarters and back again. The resulting oscillatory changes in arterial blood pressure (BP), cardiac output, stroke volume, heart rate (HR), and peripheral resistance (PR) were analyzed using a fast Fourier transform. Normal dogs were superior to cardiac-denervated dogs in minimizing arterial BP fluctuations, especially in the midfrequency range (i.e., approximately 0.032 Hz); after pharmacological alpha-, beta-, and muscarinic-receptor blockade, the BP oscillations were similar in the two groups. The unblocked denervated dogs regulated BP poorly primarily because of their inability to 1) make appropriately timed changes in HR and 2) minimize inappropriate oscillations in SV. Both groups of dogs in the unblocked state showed large appropriately timed PR fluctuations at the lower frequencies, which minimized BP oscillations; these became less optimally timed as acceleration frequency increased, thereby potentiating the natural disposition for BP to oscillate at the acceleration frequency. Afferent information from cardiac receptors did not appear to be essential for controlling this aspect of vascular function.
Refined membrane preparations mask ischemic fall in myocardial beta-receptor density
Authors: Wolff A. A. , Hines D. K. , Karliner J. S.
Published: December 2017

Most of the previous studies of ischemic myocardial beta-adrenergic receptors have employed membrane preparations in which the initial pellet from the myocardial homogenate spun at a low speed was discarded. We studied changes in beta-adrenergic receptor density ([125I]-iodocyanopindolol; Bmax) during 30 min of coronary occlusion in surgically anesthetized open-chest rabbits using just such a pellet [homogenized heart spun at 1,000 g (1,000-g pellet)], as well as a second pellet from the supernatant of the first pellet [spun at 40,000 g (40,000-g pellet)]. Bmax fell during acute ischemia in the 1,000-g pellet [46.8 +/- 6.1 vs. 21.6 +/- 2.4 (SE) fmol/mg protein; P less than 0.01; n = 7] but did not change in the 40,000-g pellet [46.8 +/- 6.5 vs. 47.9 +/- 2.6 (SE) fmol/mg protein; P = NS; n = 6]. The 1,000-g pellet contained 70.0 +/- 8.1% of the beta-adrenergic receptors measured between the two preparations (P less than 0.05; n = 8) and all of the histamine H2-receptors; therefore, to minimize receptor loss and other potential artifacts, unspun myocardial homogenate was studied. An ischemic decrease in Bmax was still observed [32.9 +/- 2.0 vs. 20.9 +/- 4.1 (SE) fmol/mg protein; P less than 0.05; n = 5]. These results support the use of data from cruder myocardial membrane preparations (e.g., 1,000-g pellet or unspun homogenate), which may be of greater pathophysiological relevance than data derived from a standard more-refined preparation (40,000-g pellet).
Voltage and beat dependence of Ca2+ transient in feline ventricular myocytes
Authors: duBell W. H. , Houser S. R.
Published: December 2017

The positive contractile staircase after a period of rest is attributable to a positive staircase in the magnitude of the Ca2+ transient. The present study used voltage-clamp techniques and the fluorescent Ca2+ indicator, indo-1, to examine the effects of membrane potential, the duration of depolarization, and the slow inward Ca2+ current (Isi) in the regulation of the magnitude of the steady-state Ca2+ transient and the development of the steady state during the positive staircase. In the steady state, the Ca2+ transient was greatest at +10 mV, the potential at which Isi was also the greatest. However, the Isi-voltage relationship was much more bell-shaped than the Ca2+ transient-voltage relationship. The magnitude and duration of the steady-state Ca2+ transient was not affected by pulse durations as short as 25 ms. However, prolonged voltage pulses were essential to maintain the steady state. The development of the positive staircase was very voltage dependent. After a rest period, a positive staircase was seen when voltage-clamp drives were done to +30 mV but not when done to -10 mV, potentials that elicit Isi of comparable magnitude. These results support the idea that the early peak of Isi can act as a trigger for release of Ca2+ from the sarcoplasmic reticulum. However, sarcoplasmic reticulum Ca2+ loading is dependent on prolonged depolarization and may be mediated through Na+-Ca2+ exchange.
Brief vagal bursts can induce Wenckebach arrhythmia
Authors: Wallick D. W. , Martin P. J.
Published: December 2017

We hypothesized that a brief burst of vagal stimulation applied in each cardiac cycle could elicit an atrioventricular (AV) nodal Wenckebach arrhythmia. Twenty-six dogs were anesthetized with pentobarbital sodium (30 mg/kg iv) and were given propranolol (1 mg/kg iv). We varied the timing of a vagal stimulus burst in steps of 25-50 ms relative to the onset of atrial or ventricular depolarization. In four of nine experiments, a Wenckebach arrhythmia occurred despite changing the timing of stimuli. By prolonging the effects of vagal stimulation on AV conduction with physostigmine, the timing of the stimuli no longer influenced the severity of the arrhythmia. We did experiments to open one of the feedback control loops; these results indicated that this arrhythmia has elements of a positive feedback control system. We also studied the effects of vagal stimulation on the arrhythmia during retrograde conduction. We found that the timing of vagal stimulation was critical in eliciting the arrhythmia in only 4 of the 10 dogs.
Phorbol amplification of serotonin-induced arterial contractions is endothelium dependent
Authors: Consigny P. M.
Published: December 2017

This study determined the effect of phorbol pretreatment on serotonin [5-hydroxytryptamine (5-HT)]-induced contractions of rabbit abdominal aorta. Rings of aorta pretreated with 12-O-tetradecanoylphorbol 13-acetate (TPA, 10(-7) M) contracted more strongly (P less than 0.01) than rings pretreated with the vehicle dimethyl sulfoxide (0.0007%), but only at low 5-HT concentrations (10(-8) to 10(-7) M). A 10-min exposure to TPA (10(-7) M) increased (P less than 0.01) 5-HT contractions (10(-7) M) from 23.7 +/- 2.6 to 42.1 +/- 4.5%. This amplification required an intact endothelium and the use of a biologically active phorbol. Pretreatment with TPA (10(-7) M) reduced (P less than 0.01) acetylcholine-induced relaxations from 56.6 +/- 6.6 to 20.0 +/- 13.8%. Changes in guanosine 3',5'-cyclic monophosphate-mediated relaxation are not involved in this decrease, since relaxations to sodium nitroprusside (10(-9) to 10(-8) M) were not altered by TPA pretreatment. These results suggest that activation of protein kinase C in endothelial cells may produce arterial supersensitivity to 5-HT by decreasing the release of endothelium-derived relaxing factor(s) and/or by increasing the release of endothelium-derived contracting factor(s).
Hypothalamic influences on cardiovascular response of beagles to dynamic exercise
Authors: Ordway G. A. , Waldrop T. G. , Iwamoto G. A. , Gentile B. J.
Published: December 2017

We studied nine young adult beagles at rest and during four levels of dynamic exercise before and after electrolytic lesions were made in the hypothalamus in the region of the fields of Forel. The beagles were habituated to run freely on a motor-driven treadmill and were instrumented chronically to allow repeated measurement of cardiovascular variables. Variables measured or calculated included O2 consumption, cardiac output, arteriovenous O2 difference, systemic arterial pressure, systemic vascular resistance, heart rate, and mixed venous blood lactate concentration. In addition, regional blood flow was measured with radioactive microspheres in two beagles at rest and during peak exercise (6.4 km/h, 20% grade). After prelesion treadmill studies, the beagles were anesthetized and the tips of stainless steel electrodes were placed bilaterally in the hypothalamus in locations that when stimulated (100-300 microA) evoked increases in cardiovascular and muscle motor function. Lesioning (5 mA; 15 s) abolished the responses evoked by stimulation. By contrast, the cardiovascular variables measured in the beagles at rest and during dynamic exercise were similar pre- and postlesion. Therefore, loss of hypothalamic sites that produce increases in cardiovascular and muscle motor function when stimulated electrically does not appear to comprise the cardiovascular response of awake beagles to dynamic exercise.
Effects of intracardiac bradykinin and capsaicin on spinal and spinoreticular neurons
Authors: Bolser D. C. , Chandler M. J. , Garrison D. W. , Foreman R. D.
Published: December 2017

The responses of thoracic spinal and spinoreticular tract (SRT) neurons to activation of cardiac spinal afferents by injections of bradykinin (BK) and capsaicin (CAP) into the left atrium or pericardial sac were determined in vagotomized cats anesthetized with alpha-chloralose. Activities of spinal and SRT neurons in the T1-T5 spinal cord were recorded extracellularly. All neurons received excitatory somatic and cardiopulmonary sympathetic afferent input. Application of BK and CAP to the heart excited most SRT neurons and many spinal neurons but also inhibited some spinal neurons. The two drugs often affected spinal but not SRT neurons differently. Capsaicin excited high threshold and high threshold inhibitory neurons but not wide-dynamic range spinal neurons. In contrast, BK excited all three categories of spinal and SRT neurons. The differential responses of spinal neurons to intracardiac BK and CAP suggested that these compounds can stimulate functionally different populations of cardiac sympathetic afferents.
Adenosine and cerebral capillary perfusion and blood flow during middle cerebral artery occlusion
Authors: Anwar M. , Weiss H. R.
Published: December 2017

The effects of adenosine on regional cerebral blood flow and indexes of the total and perfused microvascular bed were studied after 1 h of middle cerebral artery occlusion in the anesthetized rat. Iodo[14C]antipyrine was used to determine cerebral blood flow. Fluorescein isothiocyanate-dextran was used to study the perfused microvasculature, and an alkaline phosphatase stain was used to identify the total bed. Mean arterial blood pressure was significantly reduced by adenosine. Cerebral blood flow increased significantly by 75%, except in the flow-restricted cortex where flow averaged 28 +/- 15 (SD) ml.min-1.100 g-1 in control and 34 +/- 33 ml.min-1.100 g-1 in adenosine-treated animals. No significant regional structural differences were observed within the microvascular beds of the two groups. The percentage of the microvascular volume perfused increased significantly in all brain regions in the adenosine-treated rats, including the flow-restricted cortex. The percent perfused arteriolar volume in the flow-restricted cortex was 30 +/- 12% in control and 95 +/- 3% in adenosine-treated animals. Similar values for the capillary bed were 22 +/- 10% in control and 54 +/- 3% in adenosine-treated rats. These results indicate a maintenance of flow with a reduction in diffusion distances in the flow-restricted cortex after treatment with adenosine.
Superoxide mediates reperfusion-induced leukocyte-endothelial cell interactions
Authors: Suzuki M. , Inauen W. , Kvietys P. R. , Grisham M. B. , Meininger C. , Schelling M. E. , Granger H. J. , Granger D. N.
Published: December 2017

The objective of this study was to determine whether superoxide mediates the leukocyte-endothelial cell interactions elicited by reperfusion (reoxygenation) of ischemic (hypoxic) tissues. Mesenteric and intestinal blood flows were reduced to 20% of control for 1 h, followed by 1 h of reperfusion. Sixty minutes after reperfusion, red blood cell velocity (Vr), leukocyte rolling velocity (Vw), and the number of adherent leukocytes were measured in mesenteric venules. Then, either human superoxide dismutase (hSOD), hydrogen peroxide-inactivated hSOD, or MoAb IB4 (a monoclonal antibody against the leukocyte adhesion molecule CD18) was injected intravenously. Ten minutes later, repeat measurements were obtained and compared with pretreatment values. hSOD attenuated reperfusion-induced neutrophil adherence and increased Vw/Vr, an index of the fracture stress between leukocytes and endothelium. Peroxide-inactivated hSOD did not alter any parameter. MoAb IB4 attenuated reperfusion-induced adherence but did not alter Vw/Vr. In a correlate study, cultured bovine microvascular endothelium was exposed to 30 min of anoxia, followed by 60 min of reoxygenation. Cat neutrophils were added during reoxygenation. Reoxygenation-induced leukocyte adherence was attenuated by either hSOD or MoAb IB4 but not by inactivated hSOD. Adherence of phorbol 12-myristate 13-acetate-activated cat neutrophils to plastic was unaffected by hSOD or inactive hSOD, yet MoAb IB4 virtually abolished the response. These results indicate that superoxide mediates reperfusion-induced leukocyte adherence and that endothelial cells are required for this superoxide-mediated adherence.
Role of xanthine oxidase in postischemic microvascular injury in skeletal muscle
Authors: Smith J. K. , Carden D. L. , Korthuis R. J.
Published: December 2017

Previous reports indicate that allopurinol, a xanthine oxidase inhibitor, attenuates the microvascular injury produced by reperfusion of ischemic skeletal muscle. To further assess the role of xanthine oxidase in ischemia/reperfusion (I/R) injury, we examined the effect of xanthine oxidase depletion or inhibition on the increase in microvascular permeability produced by I/R. Changes in vascular permeability were assessed by measurement of the solvent drag reflection coefficient for total plasma proteins (sigma) in rat hindquarters subjected to 2 h of ischemia and 30 min of reperfusion in xanthine oxidase-replete and -depleted animals and in animals pretreated with the xanthine oxidase inhibitor oxypurinol. Xanthine oxidase depletion was accomplished by administration of a tungsten-supplemented (0.7 g/kg diet), molybdenum-deficient diet. In animals fed the tungsten diet, muscle total xanthine dehydrogenase plus xanthine oxidase activity was decreased to less than 10% of control values. Estimates of sigma averaged 0.85 +/- 0.04 in nonischemic (continuous perfusion for 2.5 h) hindquarters, whereas muscle xanthine oxidase activity averaged 3.3 +/- 0.4 mU/g wet wt. I/R was associated with a marked decrease in sigma (0.54 +/- 0.02), whereas xanthine oxidase activity was increased to 5.8 +/- 0.5 mU/g wet wt. These results indicate that I/R produced a dramatic increase in vascular permeability coincident with an increase in muscle xanthine oxidase activity. Xanthine oxidase depletion with the tungsten diet or pretreatment with oxypurinol attenuated this permeability increase (sigma = 0.72 +/- 0.03 and 0.77 +/- 0.7, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of ischemia on brain blood flow and oxygen consumption of newborn pigs
Authors: Leffler C. W. , Busija D. W. , Mirro R. , Armstead W. M. , Beasley D. G.
Published: December 2017

Brain circulation after 20 min of total brain ischemia was examined in unanesthetized newborn pigs. Except in the cerebrum, reactive hyperemia was observed throughout the brain, peaking by 5 min and subsiding by 20 min of reperfusion. Brain blood flow after 15 min of reperfusion matched the control. Blood flow to the cerebrum then decreased at 40 and 90 min reperfusion, while the rest of the brain was unaffected. Blood flow to the cerebrum returned to control by 24 h. Cerebral vascular resistance doubled by 15 min reperfusion, remained elevated at 90 min reperfusion, but returned to control by 24 h. Cerebral oxygen consumption followed a pattern similar to blood flow. Ninety minutes postischemia, hypercapnia-induced hyperemia was greatly attenuated in the cerebrum, reduced modestly in the diencephalon-mesencephalon, but unaffected in the rest of the brain. Thus 20 min of global brain ischemia in piglets does not produce reactive hyperemia in the cerebrum that is detectable at 5 min reperfusion but does in the remainder of the brain. Subsequent hemodynamic abnormalities apparently are confined to the cerebrum. Blood flow throughout the brain returns to normal by 24 h. Thus cerebral hemodynamic effects of total global ischemia are regionally dependent.
Reflex stimulation of sympathetic outflow during rhythmic exercise in humans
Authors: Victor R. G. , Seals D. R.
Published: December 2017

The aim of this study was to determine whether a chemically generated reflex arising in nonischemic skeletal muscle normally increases sympathetic outflow during rhythmic exercise. To accomplish this aim, we recorded muscle sympathetic nerve activity (MSNA, peroneal nerve) in conscious humans during exercise interventions designed to alter the relationship between muscle blood flow and metabolic demand. Under normal conditions, MSNA increased during moderate but not during mild levels of rhythmic handgrip (0.67 Hz) and one-arm cycling (0.83 Hz). MSNA remained elevated when the moderate level of rhythmic handgrip was followed by forearm vascular occlusion, a maneuver that sustains muscle chemoreflex stimulation. Complete arm vascular occlusion was needed to increase MSNA during mild arm cycling, whereas even partial vascular occlusion greatly amplified the stimulation of MSNA normally produced by the moderate level of arm cycling. We conclude that a chemically generated reflex arising in nonischemic working muscle plays an important role in the normal activation of sympathetic discharge to nonexercising leg muscles during moderate but not during mild levels of rhythmic arm exercise.
Membrane resistance increases when automaticity develops in explanted rat heart cells
Authors: Schanne O. F. , Lefloch M. , Fermini B. , Ruiz-Petrich E.
Published: December 2017

We compared the passive electrical properties of isolated ventricular myocytes (resting potential -65 mV, fast action potentials, and no spontaneous activity) with those of 2- to 7-day-old cultured ventricle cells from neonatal rats (resting potential -50 mV, slow action potentials, and presence of spontaneous activity). In myocytes the specific membrane capacity was 0.99 microF/cm2, and the specific membrane resistance increased from 2.46 k omega.cm2 at -65 mV to 7.30 k omega.cm2 at -30 mV. In clusters, the current-voltage relationships measured under current-clamp conditions showed anomalous rectification and the input resistance decreased from 1.05 to 0.48 M omega when external K+ concentration was increased from 6 to 100 mM. Using the model of a finite disk we determined the specific membrane resistance (12.9 k omega.cm2), the effective membrane capacity (17.8 microF/cm2), and the lumped resistivity of the disk interior (1,964 omega.cm). We conclude that 1) the voltage dependence of the specific membrane resistance cannot completely explain the membrane resistance increase that accompanies the appearance of spontaneous activity; 2) a decrease of the inwardly rectifying conductance (gk1) is mainly responsible for the increase in the specific membrane resistance and depolarization; and 3) approximately 41% of the inward-rectifying channels are electrically silent when spontaneous activity develops in explanted ventricle cells.
Analysis of vasomotion waveform changes during pressure reduction and adenosine application
Authors: Oude Vrielink H. H. , Slaaf D. W. , Tangelder G. J. , Weijmer-Van Velzen S. , Reneman R. S.
Published: December 2017

Changes in the vasomotion waveform were studied in transverse arterioles (TAs) and their first-order side branches (FOSs) in the tenuissimus muscle of 14 young, anesthetized rabbits during stepwise arterial pressure reduction and local application of adenosine using intravital video microscopy. Pressure reduction resulted in a systematic increase in vasomotion cycle length (CL) and amplitude (A) concomitant with an increase in effective vascular diameter (Deff) and maximum diameter and a decrease in blood flow (Q). During adenosine application Deff and maximum diameter also increased, but CL and A did not change systematically. At moderate pressure reductions and during adenosine application CL changes were limited (less than 1.5 s) and nonsystematic, agreeing with an earlier study (D. W. Slaaf, G. J. Tangelder, H. C. Teirlinck, and R. S. Reneman. Microvasc. Res. 33: 71–80, 1987). In TAs these changes resulted from changes in both the dilation and the constriction phase. In FOSs, however, changes in CL were caused by prolongation of the dilation phase alone. At greatly reduced pressure levels, the CL increase was more pronounced and in both TAs and FOSs was caused by plateau formation in the dilation phase. Stretch of the arteriolar wall does not seem to play a role in control of the vasomotion waveform. Because the onsets of dilation always occur synchronously in TAs and FOSs, but the onsets of constriction do not, vasomotion seems to be a series of rhythmic dilations.
ATP-dependent decay and recovery of K+ channels in guinea pig cardiac myocytes
Authors: Takano M. , Qin D. Y. , Noma A.
Published: December 2017

ATP-dependent decay and recovery of the inward rectifier and ATP-sensitive K+ channels were investigated using inside-out patch recording in cardiac myocytes. The solution facing the inner side of the membrane was instantaneously changed with the oil-gate concentration jump method. Both channels were decayed by removing ATP and were recovered by reapplying ATP. The coexistence of Mg2+ was required for the recovery. 5'-Adenylylimidodiphosphate failed to reverse the ATP-dependent decay. The cumulative histograms of survival time and recovery time, obtained from the inward rectifier K+ channel, showed a single exponential distribution, time constants of which were 55 and 43 s, respectively. The time-dependent nature of decay and recovery was also confirmed in the ATP-sensitive K+ channel. The findings indicated that intracellular ATP is one of the factors that determines the activity of the K+ channels. It is most probable that phosphorylation of channel molecules is essential for maintaining the K+ channel in an operative state.
Effects of acidosis and alkalosis on hypoxic pulmonary vasoconstriction in dogs
Authors: Brimioulle S. , Lejeune P. , Vachiery J. L. , Leeman M. , Melot C. , Naeije R.
Published: December 2017

We studied the effects of metabolic and respiratory acidosis (pH 7.20) and alkalosis (pH 7.60) on pulmonary vascular tone in 32 pentobarbital-anesthetized dogs ventilated with hyperoxia (inspired oxygen fraction, FIO2 0.40) and with hypoxia (FIO2 0.10). Ventilation, pulmonary capillary wedge pressure (Ppw), and cardiac output (3 l.min–1.m-2) were maintained constant to prevent passive changes in pulmonary arterial pressure (Ppa). Metabolic acidosis and alkalosis were induced with HCl (2 mmol.kg-1.h-1) and NaHCO3-Na2CO3 (5 mmol.kg-1.h-1) infusions, respectively, and respiratory acidosis and alkalosis by modifying the inspiratory CO2 fraction. The hypoxia-induced rise in Ppa-Ppw gradient increased from 5 to 9 mmHg in metabolic acidosis (P less than 0.001), decreased from 6 to 1 mmHg in metabolic alkalosis (P less than 0.001), remained unchanged in respiratory acidosis, and decreased from 5 to 2 mmHg in respiratory alkalosis (P less than 0.001). Linear relationships were found between pH and Ppa-Ppw gradients. These data indicate that in intact anesthetized dogs, metabolic acidosis and alkalosis, respectively, enhance and reverse hypoxic pulmonary vasoconstriction (HPV). Respiratory acidosis did not affect HPV and respiratory alkalosis blunted HPV, which suggests an pH-independent vasodilating effect of CO2.
Energetic response of coronary endothelial cells to hypoxia
Authors: Mertens S. , Noll T. , Spahr R. , Krutzfeldt A. , Piper H. M.
Published: December 2017

The response of endothelial energy metabolism to oxygen supply was studied in cultured coronary endothelial cells from the rat at defined PO2 levels between 0.1 and 100 Torr. In the presence of glucose (5 mM), endothelial respiration (4 nmol O2.min-1.mg protein-1) was independent of the exterior PO2 greater than 3 Torr; oxygen consumption was half maximal at 0.8 Torr. At 100 Torr, lactate production was 26 nmol.min-1.mg protein-1; the decrease of the PO2 to 0.1 Torr resulted in a 2.2-fold increase in lactate production. The contents of ATP, ADP, and AMP were 21, 4, and 2 nmol/mg protein, respectively; they remained constant for 2.5-h incubations at PO2 levels between 0.1 and 100 Torr. In the presence of palmitate (100 microM) plus glutamine (0.5 mM), oxygen consumption was 8 nmol.min-1.mg protein-1 at PO2 levels greater than 3 Torr, and the half-maximal rate was again observed at 0.8 Torr. Lactate production was negligible. At PO2 levels greater than 3 Torr, the cells remained well energized. Below 3 Torr, however, the adenine nucleotide contents rapidly declined. These results demonstrate that the oxygen demand of coronary endothelial cells is low compared with the beating myocardium. In the presence of glucose, aerobic glycolysis is pronounced and the Pasteur effect small. In severe hypoxia (PO2 less than 0.1 Torr) the energetic state remained stable. In the absence of glucose, the energetic state of coronary endothelial cells is sensitive to the exterior PO2 less than 3 Torr, declining concomitantly with the decrease in respiration.
Cerebral blood flow during fastigial pressor response in cats
Authors: Williams J. L. , Murray M. A. , Schalk K. A. , Heistad D. D.
Published: December 2017

We tested the hypotheses that electrical stimulation of the fastigial nucleus increases cerebral blood flow by a dilator mechanism, impairs autoregulation during increases in arterial pressure, and attenuates increases in cerebral blood flow during acute hypertension by activation of sympathetic nerves. Cerebral blood flow was measured with microspheres in anesthetized cats during control and moderate or severe hypertension produced by stimulation of the rostral fastigial nucleus. Cervical sympathetic nerves to one cerebral hemisphere were cut to compare responses in the innervated and denervated hemispheres. Fastigial stimulation at a level that raised arterial pressure from 94 +/- 10 (mean +/- SE) to 133 +/- 6 mmHg had no significant effect on cerebral blood flow. Autoregulation was preserved because cerebral vascular resistance increased approximately 40% during the fastigial pressure response. When mean arterial pressure was raised to 189 +/- 9 mmHg by stimulation of the fastigial nucleus, cerebral blood flow increased similarly in the denervated hemisphere and the hemisphere with intact sympathetic nerves. We conclude that stimulation of the fastigial nucleus in cats does not have a direct dilator effect on cerebral vessels, does not impair autoregulation during moderate hypertension, and does not attenuate increases in cerebral blood flow during severe hypertension by activation of sympathetic pathways.
Muscle blood flow in trained rats with peripheral arterial insufficiency
Authors: Mathien G. M. , Terjung R. L.
Published: December 2017

The influence of exercise training on the recovery of muscle blood flow was assessed in rats with bilateral stenosis of the femoral artery, sufficient to limit exercise hyperemia in the distal hindlimb but not alter resting blood flow. Muscle blood flow was measured with 141Ce-labeled microspheres (15 microns) during treadmill running at 20 m/min in normal (n = 10), acute stenosed (n = 9), sedentary stenosed (n = 10) and trained stenosed (n = 13) animals. Treadmill training by a progressively intense program (up to 1 h/day, 7 days/wk for 6 wk) improved exercise tolerance evident both in duration and intensity of exercise. Total hindlimb blood flow (ml.min-1.100 g-1) was not different (P greater than 0.05) between all stenosed groups but was only 46-63% that of the normal group (P less than 0.05). Acute stenosis reduced distal blood flow to only 22% of that in the proximal hindlimb tissue. A significant (P less than 0.05) but limited recovery of distal limb blood flow (to 44% of proximal) occurred in sedentary stenosed rats after 6 wk of cage activity. Training further increased (P less than 0.05) distal limb blood flow to 69% of proximal. This partial recovery of distal limb blood flow could reflect a greater collateral vessel function or an enhanced vascularity of the distal limb tissue. Our results illustrate that peripheral adaptations occur within the ischemic hindlimb of trained animals to redistribute the limited O2 delivery to the active muscles most affected by stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Flow-dependent vasodilation of brachial artery in essential hypertension
Authors: Laurent S. , Lacolley P. , Brunel P. , Laloux B. , Pannier B. , Safar M.
Published: December 2017

Brachial artery hemodynamics including brachial artery diameter (D) and local blood flow velocity (V) was studied in 15 normotensive subjects (NT) and 19 age-matched hypertensive patients (HT) at rest using a bidimensional pulsed Doppler system during a 2-min period of distal circulatory occlusion and during reactive hyperemia. Kinetics of changes in V and D were determined during successive and reproducible maneuvers. V and D decreased significantly during distal circulatory occlusion in both groups. During reactive hyperemia, V reached similar maximum values in both groups, and D increased significantly in NT and HT. Changes in D during reactive hyperemia were positively and significantly correlated with changes in V recorded at the same level. No significant difference was found between the two groups. These results demonstrate noninvasively that there are velocity-dependent variations in the diameter of a large artery in humans and suggest that velocity-dependent vasodilation of the brachial artery is not impaired in essential hypertension.
Combined effects of autoregulation and vasoconstrictors on hindquarters vascular resistance
Authors: Meininger G. A. , Trzeciakowski J. P.
Published: December 2017

Relative contributions of local autoregulatory tone and vasoconstrictor tone to skeletal muscle vascular resistance were studied in anesthetized rats during hypertension produced by vasoconstrictor infusion. Rats were instrumented with a Doppler flow probe on the sacral aorta (SA) to measure blood flow and to allow calculation of vascular resistance. An occluder was placed on the SA and used to produce stepwise reductions in local perfusion pressure. Pressure-flow curves for the hindquarters were obtained in the absence and presence of elevated mean arterial pressure (MAP) produced by infusion of angiotensin II (ANG II; 50-1,247 ng.kg-1.min-1) or phenylephrine (PE; 2.5-12.4 micrograms.kg-1.min-1). Both ANG II and PE infusion increased MAP. For example, MAP was increased by ANG II from 91 to 134 mmHg and by PE from 89 to 156 mmHg. In addition, infusions of ANG II and PE produced dose-dependent rightward shifts in the hindquarters pressure-flow relationship. To examine the effect of pressure on the dose-response relationships of ANG II or PE, local perfusion pressure was adjusted to remain constant at various pressure levels that were independent of MAP during drug infusions. This produced a series of distinct dose-response curves with each curve defined by a different pressure level and with each characterized by a different maximum change in vascular resistance. If local perfusion pressure was not held constant but was permitted to increase with MAP, a compound dose-response curve was obtained in which the combined effects of the change in local pressure (i.e., autoregulation) and vasoconstrictor dose on vascular resistance could be discerned. These data demonstrate that hindquarters blood flow autoregulation continues to occur in the presence of vasoconstrictors. Consequently, autoregulatory mechanisms may be stimulated by any increase in MAP whether associated with systemic vasoconstrictor infusion or activation of neurohumoral pressor systems. The result is an amplified rise in local vascular resistance.
Intranephron PGE2 production in stroke-prone spontaneously hypertensive rats
Authors: Takemoto F. , Miyanoshita A. , Shimamura K. , Sunano S. , Endou H.
Published: December 2017

To investigate whether intranephron prostaglandin E2 (PGE2) production in stroke-prone spontaneously hypertensive rats (SHRSP) differs from that in Wistar-Kyoto rats (WKY), we measured PGE2 accumulation rates in microdissected nephron segments from 4- to 6- and 12- to 14-wk-old male rats by radioimmunoassay. In both young and adult WKY, PGE2 accumulation was highest in the papillary collecting duct (PCD) and outer medullary and cortical collecting tubules, intermediate in the glomerulus (Glm), medullary and cortical thick ascending limbs of Henle's loop, and distal tubule, and negligible in the proximal tubule. PGE2 accumulation in adult WKY was severalfold higher than that in young WKY. PGE2 accumulation in adult and prehypertensive young SHRSP was significantly lower than that of respective WKY in most segments, whereas urinary PGE2 excretion was significantly higher in SHRSP than in age-matched WKY. Plasma arginine vasopressin concentrations in adult SHRSP were significantly higher than in WKY. PGE2 accumulation stimulated by 5 microM arachidonic acid was significantly lower in SHRSP than in WKY in most segments of young rats but was lower only in Glm and PCD of adult rats. PGE2 accumulation stimulated by 2 microM Ca2+ ionophore A23187 was significantly lower in most segments of adult and young SHRSP. These results indicate that a decrease in renal tubular PGE2 productive activities in SHRSP might not be caused by secondary adaptation to hypertension.
Inhibition of cGMP-associated pulmonary arterial relaxation to H2O2 and O2 by ethanol
Authors: Burke-Wolin T. M. , Wolin M. S.
Published: December 2017

We have recently suggested that relaxation of isolated precontracted intrapulmonary arteries from calves to H2O2 or O2 may involve the activation of guanylate cyclase by peroxide metabolism via catalase. In this study, ethanol, an agent that modulates peroxide metabolism by catalase and selectively inhibits the activation of guanylate cyclase by H2O2 but not by nitric oxide-related activators, was employed to further investigate the role of catalase in pulmonary arterial relaxation and guanylate cyclase activation by O2 and H2O2. In precontracted pulmonary arteries, ethanol reverses H2O2-elicited relaxation and increases in guanosine 3',5'-cyclic monophosphate (cGMP) tissue levels without affecting similar responses to nitroprusside. The pulmonary arteries employed in this study show a hypoxic contraction that is associated with decreases in cGMP levels, and reoxygenation produces a somewhat phasic relaxation and a marked increase in cGMP levels. Ethanol produces an O2 tension-dependent contraction and reverses relaxation to reoxygenation associated with inhibition of O2-elicited increases in cGMP levels. Thus ethanol appears to function as a mimic of hypoxia by inhibiting relaxations elicited by O2. These findings support a hypothesized role for H2O2-dependent activation of guanylate cyclase in O2-dependent regulation of pulmonary arterial smooth muscle tone.
Long-term effects of nimodipine on pial microvasculature and systemic circulation in conscious rats
Authors: Yuan X. Q. , Smith T. L. , Prough D. S. , De Witt D. S. , Dusseau J. W. , Lynch C. D. , Fulton J. M. , Hutchins P. M.
Published: December 2017

The chronic cranial window preparation allows repeated measurements of the same pial vessels in unanesthetized rats for several weeks and correlation with 24-h monitoring of hemodynamic variables. Nimodipine (20 mg) or placebo was given via two subcutaneous pellets. Large arterioles dilated 26 and 16%, at hour 1 and days 6-13, respectively (P less than 0.02). There was an increase in number of small arterioles throughout the whole observation period with the maximal increment of 47% (P less than 0.05) at days 6-13. Maximal vasodilation with 10% CO2 indicated that the increase in number of small arterioles after administering nimodipine was not caused by the opening of previously closed vessels. The total length of small arterioles and venules increased 47 and 23% at days 6-13, respectively (P less than 0.001). These increases seem to be caused by the increases in the numbers of vessels, because the average length of the small vessels did not appear to change. This suggests that nimodipine reduces cerebral vascular resistance by causing cerebral microvessel neovascularization. Our data demonstrate that the administration of nimodipine (20 mg) is potent in dilating pial arterioles in the short-term without affecting systemic arterial pressure, and that its long-term effect results in new vessel growth.