bluuebunny/crossref_metadata_2025 huggingface dataset:
Carotid sinus baroreceptor reflex control of venular pressure-diameter relations in rat intestine
Authors: Haase E. B. , Shoukas A. A.
Published: December 2017

We tested the hypothesis that the venules of the small intestinal muscle are responsible for decreases in vascular capacitance during bilateral carotid artery occlusion. We measured microvascular venular pressure and diameter relations in 135 vessels during both control and baroreflexive conditions (bilateral carotid occlusion). Microvascular pressure was measured using a servo-null pressure system, and diameters were obtained from a video-monitoring system with a total magnification of X1,000. First-, second-, and fourth-order microvenules were studied in rat small intestinal muscle. The vessels showed an average diameter decrease of 11-12% and an increased stiffness or pressure-diameter slope of 31-53% during bilateral occlusion. We also tested whether the observed constriction during bilateral occlusion was caused by an increase in the sympathetic nerve activity to the venules and/or increased hormonal release via the baroreflex system. We studied an additional 22 microvenules before and after denervation of the preparation. Denervation eliminated any significant change in diameter or stiffness during bilateral occlusion. Based on our data, we conclude that the changes in the venular properties observed during bilateral occlusion are due to the increased sympathetic nerve activity resulting from decreased carotid sinus pressure. Intestinal venules can actively constrict to change vascular capacitance during bilateral carotid occlusion.
A new relaxing factor in supernatant of incubated rat peritoneal neutrophils
Authors: Kadota K. , Yui Y. , Hattori R. , Uchizumi H. , Kawai C.
Published: December 2017

It was found that when rat peritoneal neutrophils were added to an organ bath, they released an unstable vasoactive substance designated as neutrophil-derived relaxing factor (NDRF), which is similar to endothelium-derived relaxing factor. Besides NDRF, a more stable (activity maintained for at least 7 days at -80 degrees C) relaxing factor was found to be generated in the supernatant after the incubation of rat peritoneal neutrophils in buffer. This supernatant relaxing factor (SRF) induced an increase in the guanosine 3',5'-cyclic monophosphate content of aortic strips. Its relaxing activity was potentiated by superoxide dismutase. It was inhibited by hemoglobin, hydroquinone, or methylene blue but not by catalase or mannitol. Preincubation of polymorphonuclear neutrophils with aspirin, quinacrine, metyrapone, or AA-861 had no effect on the relaxing activity of SRF. L-Arginine dose dependently increased the relaxing activity of SRF, whereas NG-monomethyl-L-arginine (L-NMMA) decreased it, and this decrease was reversed by L-arginine. In contrast, neither L-arginine nor L-NMMA affected the relaxing activity of NDRF. These data suggest that SRF may represent a relaxing factor that is synthesized de novo from L-arginine.
Cardiovascular and renin responses to desmopressin in humans: role of prostacyclin and beta-adrenergic systems
Authors: Hasunuma K. , Yamada K. , Tamura Y. , Yoshida S.
Published: December 2017

To investigate the involvement of prostacyclin and the sympathetic nervous system in cardiovascular responses to 1-desamino-8-D-arginine vasopressin (DDAVP), a selective V2-receptor agonist, in normal subjects, DDAVP (0.4 micrograms/kg) was infused with or without indomethacin, a cyclooxygenase inhibitor, or propranolol, a beta-adrenoceptor antagonist. A decrease in blood pressure and increases in pulse rate and plasma renin activity (PRA) were observed by DDAVP infusion. Indomethacin did not influence the DDAVP-induced changes in blood pressure and pulse rate but suppressed the increases in PRA and urinary 6-ketoprostaglandin F1 alpha excretion after DDAVP infusion. Even with propranolol administration, DDAVP produced a similar decrease in blood pressure with a reduction of the increased pulse rate. The DDAVP-induced increase in PRA was not affected either. Indomethacin or propranolol alone did not affect the basal levels of the parameters. DDAVP stimulated the in vitro renin release from rabbit renal cortical slices. The stimulation was inhibited by indomethacin or d(CH2)5[D-Ile2,Ile4]AVP, a selective V2-receptor antagonist. These findings suggest that DDAVP primarily elicits vasodilation, probably through the prostacyclin-independent endothelium-derived relaxation and DDAVP also causes an increase in renin release, which would be partly attributed to the increased synthesis of prostacyclin due to vasculoendothelial V2-like receptor activation but not mainly due to an increase in sympathetic nerve activity.
Twenty-four hours of bed rest with head-down tilt: venous and arteriolar changes of limbs
Authors: Pannier B. M. , Lacolley P. J. , Gharib C. , London G. M. , Cuche J. L. , Duchier J. L. , Levy B. I. , Safar M. E.
Published: December 2017

The hemodynamic changes after 24 h of bed rest with -5 degree head-down tilt were studied in six normal subjects as a condition causing an intrathoracic shift of blood volume with a resulting urinary sodium and water loss and a subsequent reduction in total intravascular volume. Vascular resistance and venous tone of the upper and the lower limbs were investigated as were systemic hemodynamics throughout the procedure. Whereas systemic hemodynamic parameters did not change significantly, vascular resistance and venous tone of the upper and lower limbs decreased significantly up to the sixth h and then returned toward baseline values at 24 h. Systemic and forearm vasoconstriction responses to lower body negative pressure (LBNP) were studied just before and at the end of the study period. With LBNP, -5, -10, and -15 mmHg pressure levels were used to investigate mechanoreceptors in the low-pressure system, whereas the -40 mmHg pressure level was used to explore baroreceptors both in low and high pressure systems. Changes in vascular resistance in response to LBNP did not differ at the beginning and at the end of the head-down tilt, whereas an exaggerated heart rate response was observed at -40 mmHg at the end of 24 h of bed rest. The study showed that after 24 h of bed rest with -5 degree head-down tilt, the adaptative changes in venous tone and vascular resistance to blood volume reduction were altered. A dissociation between cardiac and vascular baroreflex response was observed in situations simulating tilting.
Effects of atherosclerosis and regression on vascular responses to products of activated platelets in primates
Authors: Lopez J. A. , Armstrong M. L. , Brotherton A. F. , Piegors D. J. , Heistad D. D.
Published: December 2017

We aggregated human platelets in vitro and examined vascular responses to injection of the supernatant in atherosclerotic primates. Platelets were washed, suspended, and aggregated with thrombin. Thrombin was then inactivated with D-Phe-Pro-ArgCH2Cl, and the suspension was centrifuged. The supernatant was injected intra-arterially into the perfused hindlimb within 30 s after aggregation of platelets. We studied normal cynomolgus monkeys, atherosclerotic monkeys that were fed atherogenic diet for 18 mo, and regression monkeys that were fed an atherogenic diet for 18 mo followed by a normal diet for 20 mo. Products of activated human platelets produced vasodilation in normal monkeys, as effects of platelet-derived vasodilators (presumably adenine nucleotides) may override platelet vasoconstrictor products. Vasodilator responses to platelet products were impaired in atherosclerotic monkeys, probably as a result of endothelial dysfunction. Regression of atherosclerosis restored vasodilator responses to platelet products toward normal. These data suggest that the predominant response to human platelet products is vasodilatation. Atherosclerosis impairs vasodilator responses to human platelet products, and regression of atherosclerosis restores responses toward normal.
Increase in sympathetic activity with age. II. Role of impairment of cardiopulmonary baroreflexes
Authors: Hajduczok G. , Chapleau M. W. , Abboud F. M.
Published: December 2017

We have previously shown that arterial baroreflex function is significantly impaired in a group of old beagles [G. Hajduczok, M. W. Chapleau, S. L. Johnson, and F. M. Abboud. Am. J. Physiol. 260 (Heart Circ. Physiol. 29): H1113-H1120, 1991]. In the present study, we determined whether the neural limb of the cardiopulmonary baroreflex control of renal sympathetic nerve activity (RSNA) and the interaction between the arterial and cardiopulmonary reflexes is also impaired with senescence. In the anesthetized state, the aortic nerves were sectioned and carotid sinuses were isolated bilaterally with carotid sinus pressures held at 50 mmHg in both young (1 yr) and old animals (11 yr). In response to graded volume expansion (VE) with 3% dextran (0 to 30 ml/kg iv), the gain of cardiopulmonary baroreflex control of RSNA was significantly lower in the old (5.1 +/- 3%/mmHg) compared with the young (13.4 +/- 3%/mmHg) animals. There were no significant differences in systemic vascular compliance or left ventricular mass index between the two groups. The gain of the carotid sinus baroreflex inhibition of RSNA was significantly attenuated by VE in the young group but was not affected in the old group. Bilateral vagotomy (VX) resulted in a 182 +/- 74% increase in RSNA in the young (P less than 0.05), but VX did not significantly increase RSNA in the old (12 +/- 17%). After VX, the carotid sinus baroreflex gain markedly increased by nearly eightfold in the young group (P less than 0.05) but was not altered in the old dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcium current in congestive heart failure of hamster cardiomyopathy
Authors: Rossner K. L.
Published: December 2017

L-type calcium current (ICa) was examined using the whole cell patch-clamp method in ventricular cardiomyocytes of 400- to 458-day-old cardiomyopathic (CM) Syrian hamsters (BIO 14.6 strain) that exhibited pathology consistent with congestive heart failure. Controls were comparably aged normal (N) hamsters (BIO F1B strain). At -35-mV holding potential, ICa, normalized to picofarads of membrane capacitance, was significantly lower in amplitude in cells of CM vs. N at 300-ms duration voltage command steps of -25 to +25 mV (10-mV increments from -25 to +65 mV). Estimates of reversal potential for ICa were similar between strains, whereas average maximum specific conductance was significantly greater for N than for CM. Inactivation time constants (biexponential) and the time constant for recovery from inactivation were significantly longer for CM vs. N. Steady-state activation and inactivation data were similar between strains by Boltzmann fit. Results suggest that ICa amplitude is below normal in CM, possibly due to decreased conductance or density of functional L-type channels. This may contribute to the depressed contractions in this model of congestive heart failure.
Morphometric measurements of chorioallantoic membrane vascularity: effects of hypoxia and hyperoxia
Authors: Strick D. M. , Waycaster R. L. , Montani J. P. , Gay W. J. , Adair T. H.
Published: December 2017

We studied the effects of hypoxia and hyperoxia on the angiogenesis process in the chick embryo chorioallantoic membrane (CAM) using four different morphometric measurements of vascularity. Chick eggs were incubated in various oxygen atmospheres (12, 16, 21, 45, or 70% oxygen) beginning on the 7th day of development, and vascularity was measured on the 14th day. Measurements of vascularity included vessel endpoint density (VED), length density, fractional image area, and a vascular density index. All measurements were made on blood vessels in randomly selected areas of CAM using a computerized image analysis system. An opaque colloidal carbon-albumin perfusate was used as a vascular marker. All four measurements showed that vascularity of CAM was inversely related to the oxygen tension to which the embryos were subjected. The VED, an estimate of total number of pre- and postcapillary vessels, exhibited the greatest degree of change, but overall changes in vascularity were modest. Prolonged exposure to a 12% oxygen atmosphere increased VED by approximately 16%, whereas 70% oxygen decreased VED by approximately 19% compared with room air control groups. We also studied the normal growth of CAM vasculature from days 8 to 18 of development. In these studies, the values of VED increased progressively throughout the entire period of development, whereas the other measurements of vascularity reached maximum values by the 14th day. We conclude that hypoxia stimulates angiogenesis in the CAM in a dose-related manner, hyperoxia inhibits CAM angiogenesis in a dose-related manner, and VED provides a sensitive estimate of vascularity in chick CAM throughout its development.
Effect of fluid resuscitation from endotoxin shock on lung transvascular fluid and protein exchange
Authors: Mullins R. J. , Tahamont M. V. , Bell D. R. , Malik A. B.
Published: December 2017

The hypothesis that volume expansion during septic shock produces a greater transvascular protein flux than volume expansion alone was tested in anesthetized sheep by giving a high dose of endotoxin (40 micrograms/kg) intravenously. After 0.5 h of systemic hypotension, Ringer lactate, equivalent to 8% body wt, was infused followed by an additional 4 h of lymph collection. The results were compared with those from control animals receiving only Ringer lactate. The changes in plasma total protein with time were similar between groups. The increases in lymph flow and lymph protein flux were greater in the endotoxin-challenged group compared with the control group receiving Ringer lactate during the first 2 h but were similar thereafter. The interstitial volume was greater in the endotoxin-challenged animals compared with controls. The extravascular masses or apparent tissue concentrations for albumin or immunoglobulin G did not change in either group receiving Ringer lactate. The pulmonary edema following resuscitation from septic shock with Ringer lactate could be accounted for by either the pulmonary hypertensive effects of endotoxin or an initial, transient increase in microvascular protein permeability but not a sustained increase in microvascular permeability.
Age-related cerebrovascular reactivity to CO2 after cerebral ischemia in swine
Authors: Helfaer M. A. , Kirsch J. R. , Haun S. E. , Koehler R. C. , Traystman R. J.
Published: December 2017

We tested the hypothesis that cerebral blood flow (CBF) reactivity to CO2 after global ischemia takes longer to recover in 1- to 2-wk-old piglets than in 6- to 10-mo-old pigs. All animals were sedated with ketamine and anesthetized with pentobarbital sodium. Cerebral ischemia was produced by sequentially tightening ligatures around the inferior vena cava and ascending aorta for 10 min. The microsphere-determined CBF response to hypercapnia (arterial PCO2 approximately 65 mmHg) was depressed at 60 min of reperfusion (9 +/- 6% of preischemia; means +/- SE) and remained depressed at 120 min (33 +/- 23% of preischemia, means +/- SE) in young pigs. In older pigs, the response was also depressed at 60 min of reperfusion (21 +/- 9% of preischemia) but was not depressed at 120 min. The pattern for recovery of hypercapnic reactivity was present in most brain regions except cerebellum, where CO2 reactivity returned to control in young animals by 120 min of reperfusion. The response to hypocapnia (arterial PCO2 approximately 25 mmHg) was also better preserved in older pigs. In older pigs recovery of CO2 reactivity during reperfusion paralleled recovery of cerebral O2 consumption over time. We conclude that older pigs have quicker return of CBF CO2 reactivity following transient global ischemia, which may be due to age-related differences in mechanisms of vascular reactivity.
NADH measurements in adult rat myocytes during simulated ischemia
Authors: Esumi K. , Nishida M. , Shaw D. , Smith T. W. , Marsh J. D.
Published: December 2017

In isolated adult rat myocytes, we tested the hypothesis that metabolic inhibition and simulated ischemia regulate the NADH/NAD+ redox couple with concomitant impairment of energy-dependent process, including contraction and maintenance of high-energy phosphate stores. We developed a method to examine the relationship among the redox couple, ATP content, and contractile performance in single cells under several conditions analogous to myocardial ischemia, with and without reperfusion. Myocytes were paced at 1 Hz while cell contraction and NADH fluorescence were determined simultaneously for single cells at 37 degrees C. Cells were exposed to cyanide and 2-deoxy-D-glucose (metabolic inhibition) or to metabolic inhibition plus 12 mM KCl and 20 mM lactate at pH 6.5 (simulated ischemia). Pyridine nucleotide fluorescence signals from single cells studied in this fashion could be modulated by metabolic inhibitors in a manner similar to that classically described for isolated mitochondria. Metabolic inhibition or simulated ischemia quickly produced maximal reduction of NAD+ to NADH. When cells were exposed to simulated ischemia for 10 min, then superfused with glucose-containing control buffer, 28% of cells exposed to conditions of simulated ischemia developed hypercontracture on reperfusion. Hypercontracture developed despite mitochondrial electron transport being reestablished. When myocyte suspensions in a cuvette were studied spectrofluorimetrically, the pyridine nucleotide fluorescence response to metabolic inhibitors was similar to that for a single cell. This permitted correlation of ATP determinations on cells in suspension with contractile and fluorescence measurements from single myocytes. In the absence of glycolysis there is correspondence among loss of electron transport, decline in high-energy phosphate concentration, and decline in contraction. Irreversible disruption of the electron transport process does not appear to be an early event in ischemic injury.
Local blood flow and glucose uptake within resting and exercising rabbit skeletal muscle
Authors: Iversen P. O. , Nicolaysen G.
Published: December 2017

A marked regional heterogeneity in blood flow at the level of large arterioles or small arteries is present within single skeletal muscles both in the dog and in the rabbit. A corresponding regional heterogeneity in metabolic activity could explain this phenomenon. We studied the correlation between regional blood flow and regional uptake of glucose within single muscles. Blood flow and glucose uptake were measured using the microsphere technique and the deoxyglucose method, respectively. Blood flow and glucose uptake were determined in 0.25-g regions from resting and stimulated muscles in anesthetized rabbits. Under resting conditions, no correlation between regional blood flow and regional glucose uptake (P greater than 0.05, 12 muscles) was observed. During stimulation, regional blood flow was positively correlated (0.4 less than r less than 0.6, P less than 0.05, 12 muscles) with regional glucose uptake. The coefficients of variation for regional blood flow and regional glucose uptake averaged approximately 0.35 and 0.23, respectively, both at rest and during stimulation. Specific fiber type distributions could not explain either the regional heterogeneity in blood flow or in glucose uptake. We conclude that regional blood flow within single skeletal muscles is not strongly linked to regional uptake of glucose. Both variables show considerable heterogeneity.
High-speed digital imaging of cytosolic Ca2+ and contraction in single cardiomyocytes
Authors: O'Rourke Brian , Reibel Diane K. , Thomas Andrew P.
Published: December 2017

Pages H230–H241: Brian O'Rourke, Diane K. Reibel, and Andrew P. Thomas. “High-speed digital imaging of cytosolic Ca2+ and contraction in single cardiomyocytes.” We regret that the authors' corrections were not included in the final proof.

(See PDF)

Page H237: Table 2 should appear as the following:

(See PDf)
Variation in local cerebral blood flow response to high-dose pentobarbital sodium in the rat
Authors: Otsuka T. , Wei L. , Acuff V. R. , Shimizu A. , Pettigrew K. D. , Patlak C. S. , Fenstermacher J. D.
Published: December 2017

Microvascular bed structure and functions are known to vary throughout the brain. Microvascular responses to high doses of pentobarbital sodium might therefore differ among brain areas. This possibility was examined by measuring local cerebral blood flow (LCBF) with [14C]iodoantipyrine in 52 brain areas at 5, 10, 25, and 60 min after intraperitoneal administration of pentobarbital (50 mg/kg). From 5 to 60 min, LCBF was significantly lowered in 17 of 25 forebrain gray matter areas but in only 1 of 18 hindbrain gray matter structures, the pontine nuclei. Smaller, shorter duration lowering of LCBF was also observed in ten other brain areas. In both control and treated rats, LCBF was found to vary within individual brain structures. The pattern of these LCBF variations was columnar in the cerebral cortex and the hippocampus but was patchy in the caudate-putamen, thalamus, and inferior colliculus. These results indicate that pentobarbital anesthesia more strongly alters LCBF in the forebrain than in the hindbrain and produces different patterns of changes in LCBF than in local cerebral glucose utilization, which was measured with 2-deoxyglucose in a companion study.
Release of endothelium-derived relaxing factor is modulated both by frequency and amplitude of pulsatile flow
Authors: Hutcheson I. R. , Griffith T. M.
Published: December 2017

We have dissociated the effects of frequency and amplitude of pulsatile flow on flow-induced release of endothelium-derived relaxing factor (EDRF) using cascade bioassay. Rat aortic segments were buffer perfused with a peristaltic pump at a constant mean flow rate of 9 ml/min. EDRF activity in effluent was measured by relaxation of endothelium-denuded rabbit aortic rings preconstricted by phenylephrine. Pulse frequency was varied over the range 0.1-12 Hz at a constant amplitude of 2 mmHg; pulse amplitude was varied over the range 2-16 mmHg at a constant frequency of 0.1 Hz. Relaxation of the detector vessel depended on frequency of flow through the donor; peak response occurred between 4.2 and 6 Hz and was approximately three times greater than that induced at lower or higher frequencies. In contrast, increases in pulse pressure amplitude (maximum 16 mmHg) monotonically augmented constriction of partially preconstricted detector tissue by up to 10%. Incubation of the donor vessel with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, or removal of its endothelium by rubbing, abolished both the frequency- and the amplitude-dependent effects observed in the detector tissue, indicating that these were mediated by changes in EDRF release. Increasing the amplitude of the pressure pulse also reduced mean perfusion pressure (by up to 50%), implying distension of donor vessel since mean flow rate was constant. This fall in pressure was not affected by incubation with L-NAME or removal of endothelium, indicating that it was not dependent on EDRF activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of alpha 1-adrenergic blockade on myocardial blood flow during exercise after myocardial infarction
Authors: Herzog C. A. , Dai X. Z. , Bache R. J.
Published: December 2017

The effect of alpha 1-adrenergic blockade with prazosin on myocardial blood flow at rest and during two levels of treadmill exercise was assessed in 16 chronically instrumented dogs 9-14 days after myocardial infarction had been produced by occlusion of the left circumflex coronary artery. During resting conditions prazosin did not alter mean myocardial blood flow or the subendocardial-to-subepicardial flow ratio in either normally perfused or collateral-dependent myocardium. However, during exercise at comparable external work loads and comparable rate-pressure products, prazosin significantly increased blood flow to normally perfused (27% increase at the second level of exercise, P less than 0.001) and collateral-dependent myocardium (35% increase at the second level of exercise, P less than 0.001) compared with control. In addition, prazosin caused a small but significant decrease in the subendocardial-to-subepicardial flow ratio in both normal (1.27 +/- 0.04 to 1.19 +/- 0.04; P less than 0.01) and collateral-dependent myocardium (0.57 +/- 0.11 to 0.52 +/- 0.11; P less than 0.01) compared with control, reflecting a disproportionally greater increase in subepicardial flow in response to alpha 1-adrenergic blockade. These data demonstrate that alpha 1-adrenergic vasoconstriction inhibits coronary vasodilation during exercise, even in areas of collateral-dependent myocardium relatively early after coronary artery occlusion.
Correlation of myocardial necrosis with kinetics of 111In-labeled myosin-specific antibody in isolated rabbit septum
Authors: Williams B. A. , Huang S. C. , Krivokapich J. , Buxton D. B. , Schelbert H. R.
Published: December 2017

Radiolabeled monoclonal antibody fragments to myosin, specifically 111In-labeled antimyosin, have been shown to be effective for imaging areas of myocardial infarct. To determine if 111In-labeled antimyosin can be used to assess the extent of necrosis, we compared the tissue retention fraction of 111In-labeled antimyosin with the amount of creatine kinase (CK) released from the isolated, perfused, interventricular rabbit septum after an intervention to induce tissue necrosis. 111In-labeled antimyosin was injected and tissue radioactivity was monitored for a 60-min period under control conditions. Effluent samples were also collected during this period and assayed for CK content. After a period of Ca2+ depletion followed by Ca2+ repletion, 111In-labeled antimyosin was again injected, and washout and CK data were collected. Comparison of the changes in 111In-labeled antimyosin retention fraction from control to intervention with the corresponding increase in CK released during intervention resulted in a correlation coefficient of 0.83. To corroborate the findings of the Ca2+ depletion followed by repletion experiments, further experiments were conducted in which zero-flow ischemia followed by reperfusion was used as a means of introducing necrosis in the septum. The resulting correlation coefficient between CK release and 111In-labeled antimyosin retention fraction was 0.82. The results of these experiments indicate that 111In-labeled antimyosin can be used to quantitatively estimate the extent of necrosis in the rabbit septum, as determined by CK release, and endorse the potential use of tracer kinetics in humans for quantitation of myocardial necrosis in vivo.
Activated oxygen species do not mediate hypercapnia-induced cerebral vasodilation in newborn pigs
Authors: Leffler C. W. , Mirro R. , Thompson C. , Shibata M. , Armstead W. M. , Pourcyrous M. , Thelin O.
Published: December 2017

In newborn pigs, vasodilation in response to hypercapnia is dependent on prostaglandin (PG) H synthase. We investigated the contribution of activated oxygen by-products to hypercapnia-induced PGH synthase-dependent dilation of pial arteries and arterioles in anesthetized newborn pigs. Activated oxygen species were generated on the cerebral surface using xanthine oxidase and hypoxanthine. Catalase, H2O2, and iron or N-(2-mercaptopropionyl)-glycine (MPG) were used to separate effects of superoxide anion and hydroxyl radical. All the activated oxygen species tested caused vasodilation of both arteries and arterioles. Vasodilation to all activated oxygen species was largely reversible with only the hydroxyl radical encouraging combination of xanthine oxidase, hypoxanthine, H2O2, and FeCl3, causing significant dilation 20 min after removal of treatment. Cotreatment with MPG blocked this residual dilation. Neither pretreatment with the extracellular superoxide anion radical scavenger, superoxide dismutase (SOD), the intracellular superoxide anion radical scavenger, Tiron, the H2O2 scavenger, catalase, nor hydroxyl radical scavengers, dimethyl sulfoxide (DMSO) and MPG, altered vasodilation of pial arteries or arterioles in response to hypercapnia. Furthermore, the increase in cerebral prostanoid synthesis in response to hypercapnia was not affected by pretreatment with SOD, Tiron, catalase, DMSO, or MPG. We conclude that the progressively reduced forms of oxygen that would be produced during PGH synthase metabolism of arachidonic acid can dilate pial arteries and arterioles of newborn pigs. However, these activated oxygen species are not responsible for the vasodilation to hypercapnia in the newborn pig, suggesting that eicosanoids cause the dilation.
Periodicities of cardiac mechanics
Authors: Ben-Haim S. A. , Fruchter G. , Hayam G. , Edoute Y.
Published: December 2017

Using a finite-difference equation to model cardiac mechanics, we simulated the stable action of the left ventricle. This model describes the left ventricular end-diastolic volume as a function of the previous end-diastolic volume and several physiological parameters describing the mechanical properties and hemodynamic loading conditions of the heart. Our theoretical simulations demonstrated that transitions (bifurcations) can occur between different modes of dynamic organization of the isolated working heart as parameters are changed. Different regions in the parameter space are characterized by different stable limit cycle periodicities. Experimental studies carried out in an isolated working rat heart model verified the model predictions. The experimental studies showed that stable periodicities were invoked by changing the parameter values in the direction suggested by the theoretical analysis. We propose in the present work that mechanical periodicities of the heart action are an inherent part of its nonlinear nature. The model predictions and experimental results are compatible with previous experimental data but may contradict several hypotheses suggested to explain the phenomenon of cardiac periodicities.
Endothelin effects in isolated, perfused lamb lungs: role of cyclooxygenase inhibition and vasomotor tone
Authors: Toga H. , Usha Raj J. , Hillyard R. , Ku B. , Anderson J.
Published: December 2017

We have determined the sites of action of endothelin-1 (ET) in the lamb pulmonary circulation. The influence of cyclooxygenase inhibition and baseline vasomotor tone on ET effects was also studied. Lungs of 14 lambs (6-9 wk of age, 12.1 +/- 0.6 kg body wt) were isolated and perfused with blood. Group I lungs (n = 5) were untreated, group II lungs (n = 5) were treated with indomethacin to inhibit cyclooxygenase, and group III lungs (n = 4) were treated with indomethacin and a thromboxane A2 analogue, U-46619, to elevate vasomotor tone. All lungs were perfused with constant flow in zone 3, with left atrial and airway pressures being 8 and 6 cmH2O, respectively. We measured pulmonary arterial pressure and, by the micropuncture servo-null method, pressures in 20- to 50-microns diameter subpleural venules, both before and after each dose of ET was infused (50, 100, 250, and 500 ng/kg). Group I lungs, with high baseline vasomotor tone, exhibited a biphasic response to ET; 50-100 ng/kg of ET dilated both arteries and veins, whereas 500 ng/kg of ET constricted both arteries and veins. In group II lungs with low vasomotor tone, all doses of ET caused constriction of arteries only. In group III lungs (indomethacin treated with elevated vasomotor tone), 50-100 ng/kg of ET caused dilation of arteries and veins, whereas 500 ng/kg of ET induced constriction, this time only in arteries. We conclude that ET has both dilator and constrictor effects in arteries and veins of isolated, perfused lamb lungs. ET-induced arterial and venous dilation is dependent on initial vasomotor tone but not on cyclooxygenase metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)
Ischemic contracture begins when anaerobic glycolysis stops: a 31P-NMR study of isolated rat hearts
Authors: Kingsley P. B. , Sako E. Y. , Yang M. Q. , Zimmer S. D. , Ugurbil K. , Foker J. E. , From A. H.
Published: December 2017

The relationships among myocardial ATP, intracellular pH, and ischemic contracture in Langendorff-perfused rat hearts were investigated by 31P nuclear magnetic resonance spectroscopy during total global normothermic ischemia while the left ventricular pressure was recorded continuously via an intraventricular balloon. Glucose-perfused hearts (n = 63) were divided into five groups based on the time of onset of contracture (TOC), and three other groups of hearts were treated to vary the ischemic glycogen availability. ATP levels, which showed no evidence of accelerated ATP depletion during contracture, were significant and variable at TOC. Intracellular pH initially declined and then leveled off at TOC, with lower final pH in hearts with later TOC. We conclude that contracture began when anaerobic glycolysis (and thus glycolytic ATP synthesis) stopped. These results, though consistent with the concept that ischemic contracture in normal hearts results from rigor bond formation due to low ATP levels at the myofibrils, suggest that TOC is more closely related to glycolytic ATP production than to total cellular ATP content, thus providing evidence of some degree of subcellular compartmentation or metabolite channeling. In glycolytically inhibited hearts, the quite early contracture may have a Ca2+ component.
Intracellular milieu changes associated with hypoxia impair sarcoplasmic reticulum Ca2+ transport in cardiac muscle
Authors: Zhu Y. , Nosek T. M.
Published: December 2017

The effects on sarcoplasmic reticulum (SR) Ca2+ transport of solutions mimicking the important intracellular milieu changes associated with short-term hypoxia (hypoxic solutions, as described by Kammermeier et al. J. Mol. Cell. Cardiol. 14: 267, 1982) were examined. SR Ca2+ content was estimated by measuring the magnitude of the caffeine-induced contracture in saponin-skinned rat papillary muscle. SR Ca2+ uptake was inhibited by hypoxic solutions only at loading times less than or equal to 30 s. This inhibition was primarily due to the increase in Pi. The hypoxic solutions had no effect on Ca(2+)-induced Ca2+ release from the SR. We also tested the effects of ATP-free (rigor) solutions that mimic the intracellular environment during late hypoxia and ischemia. Elevating Pi or ADP alone in rigor solution had no effect on SR Ca2+ content. However, elevating Pi and ADP (+/-Mg2+) produced a 44-48% reduction in SR Ca2+ content. This reduction is most likely due to reversal of the SR Ca2+ pump. We conclude that the changes in milieu with short-term hypoxia can depress contractility in intact cardiac muscle by inhibiting SR Ca2+ uptake. During long-term hypoxia or ischemia, these milieu changes can elevate intracellular Ca2+ by reversing the SR Ca2+ pump.
Selective production of endothelium-derived nitric oxide in canine femoral veins
Authors: Miller V. M.
Published: December 2017

In arteries, analogues of L-arginine inhibit the synthesis of nitric oxide and thereby reduce endothelium-dependent relaxations. Experiments were designed to determine whether analogues of L-arginine affect endothelium-dependent responses in a systemic vein. Rings cut from canine femoral arteries and veins were suspended for the measurement of isometric force in organ chambers. In some rings, the endothelium was deliberately removed. All experiments were conducted in the presence of indomethacin (10(-5) M). NG-monomethyl-L-arginine (L-NMMA, 10(-4) M) reduced significantly endothelium-dependent relaxations to acetylcholine, ADP, and thrombin in arteries but not in veins. In the veins, the alpha 2-adrenergic agonist BHT-920 caused contractions which were reduced in rings with endothelium. L-NMMA eliminated the difference in contraction between rings with and without endothelium in the veins. This effect was reversed by L- but not D-arginine (3 x 10(-4) M). N omega-nitro-L-arginine (10(-4) M) reduced endothelium-dependent relaxations to acetylcholine, thrombin, and the calcium ionophore A23187 in venous rings. However, it did not alter the contractions to BHT-920 in rings with or without endothelium. L-Canavanine did not alter endothelium-dependent relaxations in the veins. These results suggest that synthesis of nitric oxide is associated with stimulation of alpha 2-adrenergic, muscarinic, and thrombin receptors on venous endothelial cells. Furthermore, the analogues of L-arginine affect endothelium-dependent relaxations in canine veins differentially.
Alpha-adrenoceptors in human resistance arteries from colon, pericardial fat, and skeletal muscle
Authors: Nielsen H. , Hasenkam J. M. , Pilegaard H. K. , Mortensen F. V. , Mulvany M. J.
Published: December 2017

Human resistance arteries (144-332 microns diam) from colon, pericardial fat, and skeletal muscle were mounted in a myograph for measurements of isometric contractions under conditions of partial depolarization by potassium chloride. In all preparations, both phenylephrine (alpha 1-selective agonist) and B-HT 933 (alpha 2-selective agonist) evoked concentration-dependent contractions that were antagonized by the alpha 1-selective antagonist prazosin (10(-8) M) and the alpha 2-selective antagonist yohimbine (10(-7) M), respectively. The affinities (expressed as pKB values) of prazosin for the receptor mediating the responses to phenylephrine were 8.88-9.41, whereas the affinities of yohimbine for the receptor mediating the responses to B-HT 933 were 7.71-7.97. Norepinephrine (mixed alpha 1-agonist/alpha 2-agonist) also elicited concentration-dependent responses that were modestly, but significantly, antagonized by prazosin alone and yohimbine alone at the above-mentioned concentrations. The two antagonists in combination, however, effectively antagonized the responses to this agonist. These findings strongly suggest the presence of functional, postjunctional alpha 1- and alpha 2-adrenoceptors in isolated human resistance arteries from colon, pericardial fat, and skeletal muscle and that responses to norepinephrine in these vessels are mediated by both alpha-adrenoceptor subtypes.
Time course of endothelial dysfunction and myocardial injury during coronary arterial occlusion
Authors: Viehman G. E. , Ma X. L. , Lefer D. J. , Lefer A. M.
Published: December 2017

The time course of the effects of permanent myocardial ischemia without reperfusion on the coronary vascular endothelium and myocardium were investigated in anesthetized cats. The left anterior descending (LAD) coronary artery was occluded for 1.5, 3.0, 4.5, or 6.0 h. Coronary rings from the ischemic LAD and the nonischemic left circumflex (LCX) arteries were tested for their responsiveness to the endothelium-dependent vasodilators acetylcholine (ACh, 0.1-100 nM) and the calcium ionophore A23187 (1-1,000 nM), and the endothelium-independent vasodilator sodium nitrite (NaNO2, 0.1-100 microM). Vasorelaxation was not significantly impaired in response to ACh after 1.5 h of ischemia and only moderately impaired after 3.0 h of ischemia (63 +/- 5% of control). However, after 4.5 h of ischemia the ACh-induced response was decreased to 33 +/- 4% of control and further declined to 31 +/- 4% of control after 6.0 h (P less than 0.001 from 1.5 h). There was no significant decrease in LCX ring vasorelaxant responses to vasodilators at all times, and the LAD rings only showed a moderately decreased response to NaNO2 after 6.0 h of ischemia (82 +/- 4% relaxation, P less than 0.05). Transmission electron microscopy revealed very little endothelial damage at 4.5 and 6.0 h, with only some subendothelial swelling noted. Damage to the myocardium did not become significant until after 4.5 h of ischemia, and cardiac myeloperoxidase activity, indicative of neutrophil accumulation, was not significant at any time.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of calcium and cAMP on Goα expression in neonatal rat cardiac myocytes
Authors: Foster Karen A. , Robishaw Janet D.
Published: December 2017

Culturing neonatal rat cardiac myocytes in 50 mM KCl inhibits the accumulation of Go that occurs when myocytes are placed in culture. The mechanism by which high extracellular K+ inhibits Go accumulation in myocytes was investigated by measurement of the concentration of intracellular Ca2+ ([Ca2+]) and adenosine 3',5'-cyclic monophosphate concentration ([cAMP]) of control and K+-depolarized myocytes. Although intracellular [Ca2++] in K+-depolarized myocytes was twofold higher than basal intracellular [Ca2+] in control cells, the mean intracellular [Ca2+] in contracting control myocytes was comparable to that of K+-depolarized myocytes. Furthermore, myocytes cultured in low Ca2+ plus high K+ exhibited an inhibition of Go accumulation, even though intracellular [Ca2+] was 10-fold lower than that of cells cultured in normal Ca2+ plus high K+. In addition, intracellular [cAMP] of K+-depolarized myocytes was comparable to that of control cells. Moreover, dibutyryl cAMP inhibited Go accumulation in myocytes to the same extent as high K+, even though intracellular [cAMP] differed 10-fold. Thus neither intracellular Ca2+ nor cAMP appear to mediate the inhibitory effect of high K+ on Go accumulation. However, cAMP has an inhibitory effect on Goα expression that is independent of K+.

dibutyryl cAMP; fura-2; immunoblotting
Association of pulmonary artery photorelaxation with H2O2 metabolism by catalase
Authors: Wolin M. S. , Omar H. A. , Mortelliti M. P. , Cherry P. D.
Published: December 2017

We have examined the mechanism governing guanosine 3',5'-cyclic monophosphate (cGMP)-associated photoinduced relaxation elicited by long-wavelength ultraviolet (UV) light of endothelium-removed, isolated bovine pulmonary arteries. Hypoxia, produced by gassing of the organ bath solution with 95% N2-5% CO2, inhibited photorelaxation. Photorelaxation was also inhibited by cyanide (1 mM NaCN) but was potentiated by lactate (5 mM). Irradiation of bovine pulmonary arterial smooth muscle with UV light (or exposure to exogenous H2O2) stimulated cyanide-inhibitable oxidation of methanol to formaldehyde, suggesting that UV light increased H2O2 metabolism via catalase. The UV light-induced oxidation of methanol by pulmonary arterial smooth muscle was also inhibited by hypoxia. Consumption of O2 was detected when pulmonary arterial tissue was exposed to UV light, but cyanide failed to interfere with this effect, consistent with the photochemical reduction of O2 within vascular smooth muscle in a manner independent of mitochondrial respiration. We propose that photorelaxation is associated with the intracellular photochemical reduction of O2 to form H2O2, which elicits increases of vascular smooth muscle cGMP levels via the catalase-dependent activation of soluble guanylate cyclase. In addition, we hypothesize that the photooxidation of NAD(P)H could contribute to the generation of H2O2, since the enhancement of photorelaxation by lactate may originate from increased levels of NADH.
Effect of in vivo inhibition of neutrophil adherence on skeletal muscle function during ischemia in ferrets
Authors: Weselcouch E. O. , Grove R. I. , Demusz C. D. , Baird A. J.
Published: December 2017

Neutrophils are reported to play an important role in the genesis of tissue damage during reperfusion after periods of ischemia in a variety of organs and may also be involved in loss of tissue function during ischemia. To test this hypothesis, the monoclonal antibody, MoAb 60.3, which prevents the adhesion of ferret neutrophils to cultured human endothelial cells at a concentration of 30 micrograms/ml, was tested in a model of peripheral vascular disease to determine whether it would preserve skeletal muscle function during ischemia. In an anesthetized ferret the muscles of the hindlimb were stimulated electrically to contract isometrically and the force of contraction was measured. Under normal perfusion conditions the contractile force peaked within 1 or 2 min of initiation of stimulation and gradually declined to approximately 80% of peak force after 20 min. When femoral arterial pressure was reduced to 45 mmHg by partial occlusion of the abdominal aorta, peak force was reduced by 25 +/- 7%, and within 5 min the force decayed to approximately 20% of the original peak, resulting in an area under the force-time curve (AUC) of 32 +/- 5% of that seen during the normal flow period. During ischemia after treatment with MoAb 60.3 (2 mg/kg iv), peak force was 94 +/- 3% and AUC was 49 +/- 5% of that observed during the normal flow period, a significant protective effect compared with the untreated control group (P = 0.0294). When the nonneutrophil-directed monoclonal antibody, L6, was tested in this model, no protective effects were evident.(ABSTRACT TRUNCATED AT 250 WORDS)
Competition between cutaneous active vasoconstriction and active vasodilation during exercise in humans
Authors: Kellogg D. L. , Johnson J. M. , Kosiba W. A.
Published: December 2017

Cutaneous vasoconstriction occurs in response to the initiation of dynamic exercise in hyperthermia. To find whether this response was due to increased vasoconstrictor activity or to withdrawal of active vasodilator activity, blood flow monitoring with laser-Doppler flowmetry (LDF) was combined with the local iontophoresis of bretylium. Each of six male subjects had two forearm sites treated with bretylium for selective local blockade of noradrenergic vasoconstrictor nerves in skin. LDF was monitored at those sites and at two adjacent untreated sites. Mean arterial pressure (MAP) was measured, and cutaneous vascular conductance (CVC) was calculated as LDF/MAP. After iontophoresis, subjects underwent 3 min of cold stress (water-perfused suits) to verify vasoconstrictor blockade. CVC at untreated sites fell by 35.9 +/- 3.1% (P less than 0.01) and at bretylium-treated sites was not significantly changed (P greater than 0.10). During strenuous exercise in normothermia, CVC at untreated sites fell by 16.1 +/- 4.1% (P less than 0.05) and was unchanged at bretylium-treated sites (+12.7 +/- 6.6%, P greater than 0.05). Whole body heat stress was then applied. When exercise was repeated in hyperthermia, CVC at untreated sites fell by 11.6 +/- 3.8% (P less than 0.05) but was not significantly changed at bretylium-treated sites (+3.6 +/- 3.0%, P greater than 0.30). Following return to normothermia, cold stress verified the persistence of the blockade. We conclude that exercise initiation causes a cutaneous vasoconstriction largely or entirely due to enhanced active vasoconstrictor tone in both normothermia and hyperthermia. Little or no role in this response can be ascribed to reduced active vasodilator activity.
Adriamycin-induced myocardial dysfunction in vitro is mediated by free radicals
Authors: Lee V. , Randhawa A. K. , Singal P. K.
Published: December 2017

The role of free radicals in adriamycin (Adr)-induced acute myocardial changes was examined by using different antioxidants. Exposure of papillary muscles to Adr (100 microM) in a tissue bath for 60 min reduced developed force by 42%, increased lipid peroxidation by 200%, and resulted in characteristic ultrastructural changes. Catalase (4 x 10(4) U/l), an enzyme effective in the hydrolysis of hydrogen peroxide (H2O2), was more effective in maintaining the developed force than mannitol (20 mM), a hydroxyl radical scavenger. A small protection of developed force seen with superoxide dismutase (1.2 x 10(5) U/l), a quencher of superoxide radical, was evident for the first 15 min only. Only catalase and mannitol showed significant protection against Adr-induced increase in lipid peroxidation. Ultrastructural changes due to Adr alone included mitochondrial swelling, intramitochondrial granules, vacuolization, and disruption of sarcomeres. All of these changes were reduced in the presence of both catalase and mannitol, whereas superoxide dismutase was without any effect. Complete structural or functional protection was not seen with any of the antioxidants used in the study. Although both H2O2 and hydroxyl radical appear to be involved in Adr-induced deleterious effects, data on developed force also indicate that H2O2 may have a major role in mediating the acute effects of Adr in vitro.