bluuebunny/crossref_metadata_2025 huggingface dataset:
Serotonergic mechanisms mediate renal sympathoinhibition during severe hemorrhage in rats
Authors: Morgan D. A. , Thoren P. , Wilczynski E. A. , Victor R. G. , Mark A. L.
Published: December 2017

Hemorrhage in rats produces reflex decreases in heart rate (HR) and renal sympathetic nerve activity (RSNA). Because serotonergic antagonists attenuate hemorrhage-induced vagal-mediated bradycardia, we determined whether blockade of serotonin synthesis by p-chlorophenylalanine (PCPA) or of serotonin receptors with methysergide would also abolish the renal sympathoinhibition. Mean arterial pressure (MAP), HR, and RSNA were recorded in chloralose-anesthetized rats pretreated with PCPA (300 mg.kg-1.day-1 X 3 days ip, n = 12) or vehicle (0.3 ml saline, n = 9). During hemorrhage, where MAP was maintained at 50 mmHg for 8 min, vehicle-treated rats decreased HR by 27 +/- 13 beats/min and RSNA by -55 +/- 7%. In PCPA-treated rats, HR and RSNA did not change. Cervical vagotomy abolished the bradycardia and sympathoinhibition during hemorrhage. After acute administration of methysergide (400 micrograms/kg iv, n = 8) hemorrhage produced increases of RSNA, whereas vehicle (0.5 ml saline, n = 7) preserved the renal sympathoinhibition to hemorrhage in conscious rats. Finally, volume expansion (0.88 ml blood/100 g body wt) produced comparable decreases in RSNA in sinoaortic-denervated rats pretreated with PCPA (n = 11) or vehicle (n = 10) (-58 +/- 9 vs. 47 +/- 7%, respectively). We conclude that serotonergic mechanisms are critically involved in vagal afferent inhibition of RSNA during severe hemorrhage in rats.
Vascular vasopressin receptors in renal hypertensive rats
Authors: Lariviere R. , St-Louis J. , Schiffrin E. L.
Published: December 2017

We investigated the plasma concentration of [Arg8]-vasopressin (AVP), the density of AVP-binding sites on membranes from the mesenteric vascular bed, and the pressor response to AVP of the perfused mesenteric vasculature in vitro from one-kidney, one-clip (1K, 1C) and two-kidney, one-clip (2K, 1C) Goldblatt hypertensive rats. The plasma concentration of AVP was increased in 1K, 1C hypertensive rats. The density of AVP-binding sites was similar in sham-operated normotensive, in 2K, 1C hypertensive, and in uninephrectomized rats but was significantly decreased in 1K, 1C hypertensive rats (P less than 0.05). The binding affinity of AVP was similar in all experimental groups. Vasoconstrictor response to AVP was increased in 2K, 1C hypertensive rats (27% higher than sham-operated normotensive rats, P less than 0.05). Responses in 1K, 1C hypertensive rats were similar to those of uninephrectomized rats. Our results indicate that together with an increased concentration of AVP in plasma the number of vascular AVP-binding sites is decreased in 1K, 1C hypertensive rats, whereas both are unaltered in 2K, 1C hypertensive rats. Vascular AVP receptors appear to be regulated inversely to plasma AVP concentrations. Pressor responsiveness to AVP is normal in 1K, 1C hypertensive rats and exaggerated in 2K, 1C hypertensive rats. Increased vascular responsiveness to AVP may occur independently of the regulation of AVP receptors and may contribute to elevation of blood pressure in renal hypertension in the rat.
Alpha-subunit of Gs directly activates cardiac calcium channels in lipid bilayers
Authors: Imoto Y. , Yatani A. , Reeves J. P. , Codina J. , Birnbaumer L. , Brown A. M.
Published: December 2017

Specific guanine nucleotide-binding proteins (G proteins) couple receptors to calcium channels indirectly via cytoplasmic agents such as protein kinases (Birnbaumer et al., Kidney Int. 32: 514-537, 1987). Direct coupling between the stimulatory G protein from adenylyl cyclase (Gs) and calcium channels has been shown recently in inside-out cell-free membrane patches excised from guinea pig myocytes, i.e., in the absence of cytoplasm (Yatani et al., Science Wash. DC 238: 1288-1292, 1987). In these patches, single calcium channel currents were unstable, and this complicated both the experiments and their interpretation. Calcium currents are more stable when calcium channels are incorporated into planar lipid bilayers (Rosenberg et al., Science Wash. DC 231: 1564-1566, 1986), and consequently, we used the latter method to examine the direct coupling hypothesis more fully. Bovine cardiac sarcolemmal vesicles were added to the cis side of a chamber divided by a preformed planar lipid bilayer. The cytoplasmic surface faced the trans chamber and was bathed by an ATP-free minimal solution. The extracellular solution in the cis chamber contained 100 mM Ba2+, and both chambers contained the dihydropyridine agonist BAY K 8644 at 1 microM.(ABSTRACT TRUNCATED AT 250 WORDS)
Assessment of Windkessel as a model of aortic input impedance
Authors: Burkhoff D. , Alexander J. , Schipke J.
Published: December 2017

To facilitate the analysis of aortic-ventricular coupling, simplified models of aortic input properties have been developed, such as the three-element Windkessel. Even though the impedance spectrum of the Windkessel reproduces the gross features of the real aortic input impedance, it fails to reproduce many of its details. In the present study we assessed the physiological significance of the differences between real and Windkessel impedance. We measured aortic input impedance spectra from five anesthetized open-chest dogs under a wide range of conditions. For each experimentally determined spectrum we estimated the corresponding values of the best-fit Windkessel parameters. By computer simulation we imposed both the real and best-fit Windkessel impedances on a model left ventricle and assessed the differences in seven different coupling variables. The analysis indicated that the Windkessel model provides a reasonable representation of afterload for purposes of predicting stroke volume, stroke work, oxygen consumption, and systolic and diastolic aortic pressures. However, the Windkessel model significantly underestimates peak aortic flow, slightly underestimates mean arterial pressure, and, of course, does not provide realistic aortic pressure and flow waveforms.
Independent blockade of cerebral vasodilation from acetylcholine and nitric oxide
Authors: Marshall J. J. , Wei E. P. , Kontos H. A.
Published: December 2017

We investigated the mechanisms of cerebral arteriolar dilation from topical acetylcholine and the nitrovasodilators, sodium nitroprusside, nitroglycerin, and nitric oxide, in anesthetized cats equipped with cranial windows for the observation of the cerebral microcirculation. Acetylcholine-mediated dilation was eliminated by topical methylene blue. This blockade was reversed by either topical superoxide dismutase, catalase, or deferoxamine. Nitroprusside- and nitric oxide-induced dilation were not affected by methylene blue. Vasodilation from the nitrovasodilators was significantly diminished by topical nitro blue tetrazolium, but acetylcholine-mediated dilation was unaffected by nitro blue tetrazolium. Neither methylene blue nor nitro blue tetrazolium affected dilation from topical 8-bromoguanosine 3',5'-cyclic monophosphate. These data show that methylene blue selectively blocks acetylcholine-mediated endothelium-dependent dilation by generating oxygen radicals. The mechanism involved is hydroxyl radical-mediated oxidation of endothelium-derived relaxing factor. Nitro blue tetrazolium selectively blocks dilation from the endothelium-independent nitrovasodilators. The endothelium-derived relaxing factor generated by acetylcholine in the cerebral microcirculation is not nitric oxide.
Acute postburn edema: role of strongly negative interstitial fluid pressure
Authors: Lund T. , Wiig H. , Reed R. K.
Published: December 2017

Interstitial fluid hydrostatic pressure (Pif) was measured with micropipettes during the acute edema generation that followed thermal skin injury in rats. Intradermal Pif was reduced from normal level of -1 mmHg to very negative values after thermal injury. The strongly negative Pif reflects a tissue imbibition pressure created by the thermal injury. The magnitude and duration of this pressure was dependent on the extent of the injury and the availability of fluid. After in vivo injury to 10 and 40% of the total body surface area (TBSA), mean intradermal Pif was temporarily reduced to -20 and -31 mmHg, respectively. Intravenous fluid infusion resulted in a rapid return of Pif to slightly positive values. Fluid available for transfer from the circulation was reduced by inducing the injury after killing the animal (postmortem injury) and even more by the subcutaneous insertion of a plastic barrier: this led to more pronounced reductions in Pif to average minimum values of -95 and -135 mmHg, respectively. Our data show that increased tissue imbibition pressure and increased net filtration pressure (tissue mechanisms) are responsible for a major part of the acute fluid shifts into thermally injured skin. Vascular mechanisms (permeability changes and intravascular pressure) are involved in the postburn edema development but are clearly less important than hitherto believed.
Efficacy of vasodilator therapy in canine model of acute pulmonary hypertension
Authors: Priebe H. J.
Published: December 2017

This study was performed to determine 1) the effects of acute pulmonary embolization (induced by injection of autologous muscle) on right ventricular (RV) performance, coronary hemodynamics, and gas exchange; and 2) the efficacy of subsequent administration of nitroglycerin, prostaglandin E1, and hydralazine with regard to improvement in RV function and gas exchange in eight open-chest dogs. After embolization, pulmonary artery (PA) pressure and vascular resistance (PVR) increased three- to fivefold without changes in RV end-diastolic dimensions (ultrasonic dimension technique) or pressure. However, systolic dimensions increased, and stroke volume (SV) fell. Gas exchange, lung compliance, and pH worsened. Subsequent administration of nitroglycerin (5 micrograms.kg-1.min-1) and prostaglandin E1 (0.2 micrograms.kg-1.min-1) caused further decreases in SV and pH. In contrast, hydralazine (mean 0.15 mg/kg) improved myocardial segment shortening, SV, PVR, pulmonary artery flow, and gas exchange. Coronary blood flow increased by 110%. Thus in this canine model of combined pulmonary hypertension and respiratory insufficiency, nitroglycerin and prostaglandin E1 exerted no beneficial cardiopulmonary effects. In contrast, hydralazine improved regional and global RV performance and gas exchange.
Computer algorithm for modeling transmission over one or two conduction pathways through AV node
Authors: Dorveaux L. D. , Twidale N. , Robinson N. , Tonkin A. M.
Published: December 2017

The goal of this study was to develop and test models of conduction through the atrioventricular node, particularly to encompass possible transmission over multiple pathways. Output from the atrioventricular node was related to its input, the variable coupling interval of a single extrastimulus introduced to scan diastole during programmed atrial stimulation. Trials were performed three times in 15 patients after pacing for eight beats at 100 beats/min. Hyperbolic and exponential functions were used to model trial data. For conduction over a single pathway, the standard error of the estimate was less with the exponential than with the hyperbolic model. The preferred exponential model had the general form A2H2 = K1 + K2 exp(-A1A2/K3), with K1, K2, K3 being the parameters fitted. The algorithm describing transmission over two pathways minimized sums of squares of deviations from two such exponential functions, with potential "bifurcation" points between the functions being those farthest from the computed single curve of best fit. The model predicted (R2 greater than 0.90) that 43% of the trials showed single conduction pathways and the remaining 57% showed dual pathways. A cardiologist who independently examined the data discarded eight trials because of insufficient data or scatter and agreed with presence of two pathways and the point of discontinuity in plots in 81% of trials. The reasons for discordance were minor and thus the model was reasonably verified.
ATP-sensitive K+ channels are altered in hypertrophied ventricular myocytes
Authors: Cameron J. S. , Kimura S. , Jackson-Burns D. A. , Smith D. B. , Bassett A. L.
Published: December 2017

Unitary K+ currents in single cells isolated from normal and hypertrophied feline left ventricles were studied with regard to ATP sensitivity using patch-clamp single-channel recording. Data were obtained from excised inside-out membrane patches with symmetrical transmembrane K+ concentration [K+] (140 mM) at 22 +/- 1 degree C and in the absence of divalent cations. In the absence of ATP at the intracellular membrane surface, K+ channel activity was observed during depolarizing and hyperpolarizing pulses ranging from 10 to 120 mV from the K+ equilibrium potential. The current voltage (I-V) curve displayed some inward rectification, with slope conductances becoming nonlinear at strong depolarizations. Rectification was particularly pronounced in cells from hypertrophied left ventricles relative to normal. Single-channel conductance determined from the linear portion of the I-V curve was 77 pS in both groups. The channels were blocked by intracellular Ca2+ (1 mM), extracellular tetraethylammonium (TEA; less than or equal to 2 mM) or 4-aminopyridine (0.5 mM); 2 mM ATP produced a total but reversible inhibition. The effect of ATP was to reduce channel openings; conductance was unaffected. The ATP concentration [( ATP]) that induced half-maximal inhibition of channel activity was 75 microM in normal myocytes but was 250 microM in cells from hypertrophied hearts. Rapid channel activation at diminished [ATP] may provide a protective function by maintaining resting potential or promoting vasodilation in hypertrophied myocardium.
Microvascular morphometry and perfusion in renal hypertension-induced cardiac hypertrophy
Authors: Cimini C. M. , Weiss H. R.
Published: December 2017

This study examined alterations in microvascular morphometry and perfusion occurring concomitantly with changes in coronary blood flow (CBF), flow reserves, and coronary vascular resistance (CVR) in myocardial hypertrophy. New Zealand White rabbits (n = 28) with one-kidney, one-clip hypertension (1K,1C) or uninephrectomy (control) were examined 4 wk after surgery in anesthetized open-chest preparations. Animals were divided into two experimental series. In the first series, flows were determined with radioactive microspheres during rest and adenosine-induced vasodilation. In a second series, fluorescein isothiocyanate dextran (FITC-dextran) was injected to visualize the perfused arteriolar and capillary beds. The total vasculature was marked with an alkaline phosphatase stain. Mean arterial pressure was elevated in 1K,1C animals (110 +/- 7 mmHg, means +/- SE) when compared with controls (77 + 4 mmHg), and the myocardial weight was greater. Resting CBF was higher in 1K,1C animals compared with controls (227 +/- 21 vs. 168 +/- 12 ml.min-1.100 g-1), and the flow reserve was reduced. Minimal CVR was higher in 1K,1C compared with controls (0.190 +/- 0.035 vs. 0.091 +/- 0.018 mmHg.ml-1.min.100 g). The number of capillaries per squared millimeter was not different from control (2,448 + 121 vs. 2,216 +/- 132/mm2) and the percent perfused was similar (56 +/- 2 vs. 61 +/- 3%). The arteriolar density in cardiac hypertrophy was lower (1.2 +/- 0.2 vs. 2.1 +/- 0.3/mm2), and the percent perfused was higher (86 +/- 5 vs. 63 + 6%) compared with controls. Thus, in myocardial hypertrophy, the anatomical density and volume fraction of arterioles appears to be reduced, and the percentage of arterioles perfused increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Responses of contractile function to ruthenium red in rat heart
Authors: Gupta M. P. , Innes I. R. , Dhalla N. S.
Published: December 2017

Isolated rat hearts exhibited a biphasic contractile response to varying concentrations of ruthenium red. A negative inotropic effect was observed with concentrations of 0.025–0.5 microM, whereas a reversal of these initial changes toward control or even exceeding the predrug values was obtained as ruthenium red concentration was increased to 2.5 or 5.0 microM. High concentrations (12.5–25.0 microM) of ruthenium red caused a sustained contracture. In contrast, isolated frog hearts exhibited only a sustained negative inotropic effect at 0.25–12.5 microM ruthenium red. In studies with rat heart, both negative and positive inotropic effects of 2.5 microM ruthenium red were blocked either by increasing the concentration of Ca2+ (from 1.25 to 5.0 mM) or by decreasing the concentration of Na+ (from 140 to 35 mM) in the perfusion medium. The contracture induced by 12.5 microM ruthenium red was markedly inhibited when Ca2+ in the medium was lowered. The positive inotropic effect and contracture due to ruthenium red were also blocked by 1 microM of verapamil and 1.5 mM of amiloride; however, these interventions did not prevent the initial negative inotropic effect of ruthenium red. These experiments suggest the role of extracellular Ca2+ in the dose- and time-dependent effects of ruthenium red on contractile function of the rat heart. Furthermore, the positive inotropic response to ruthenium red may be related to its actions on the Na+-dependent Ca2+ movements in the cardiac cell.
Endothelial injury and vascular reactivity in monocrotaline pulmonary hypertension
Authors: Rosenberg H. C. , Rabinovitch M.
Published: December 2017

We used awake, unsedated rats with indwelling cardiovascular catheters to study the role of endothelial injury and increased pulmonary vascular reactivity in the pathogenesis of monocrotaline (MC)-induced pulmonary hypertension. Hemodynamic findings were correlated with morphometric analyses of alterations in the vascular endothelium assessed by electron microscopy and of muscularization of pulmonary arteries assessed by light microscopy. Male Sprague-Dawley rats (200–250 g) were injected with MC (60 mg/kg) or with saline vehicle. The hemodynamic response to acute hypoxia (10% O2 for 10 min) was studied at 4, 8, and 12 days postinjection. Pulmonary artery pressures and resistances (Ppa, Rp) were similar in saline- and MC-injected rats at 4 and 8 days postinjection. In response to acute hypoxia, the rise in Ppa was also similar, but there was a slight but significant rise in Rp, (P less than 0.05) in the 8-day group, due largely to a decrease in cardiac output. At 12 days after injection, base-line Ppa was increased in MC-injected rats (P less than 0.01) and there was a heightened response to hypoxia assessed both as a significant increase in Ppa and Rp (P less than 0.05 each). Endothelial injury was observed as early as 4 days postinjection with pallor and swelling evident qualitatively and by a decreased proportion of microfilaments (P less than 0.05) assessed quantitatively. By light microscopy, extension of smooth muscle into normally nonmuscularized pulmonary arteries was evident by 8 days postinjection. By 12 days postinjection there was marked extension of smooth muscle present (P less than 0.01) with medial hypertrophy of muscular arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of prostanoids in cerebrovascular responses during seizures in piglets
Authors: Busija D. W. , Leffler C. W.
Published: December 2017

We examined the role of prostanoids to bicuculline-induced seizures in newborn pigs. Using the closed cranial window method and radioimmunoassay for prostanoids, we found that pial arterioles dilated during seizures; this dilation was associated with increased cortical periarachnoid cerebrospinal fluid (CSF) levels of prostaglandin E2, 6-ketoprostaglandin F1 alpha, prostaglandin F2 alpha, and thromboxane B2. Using radioactive microspheres, we found cerebral blood flow (CBF) increased dramatically during seizures in piglets. To examine the effects of pharmacological blockade of cyclooxygenase, we determined CBF in piglets pretreated with indomethacin (5 mg/kg) and in a corresponding group of piglets made hypothermic to be sure preseizure CBF values were similar. In the hypothermic group, CBF increased during seizure, but the increase in CBF during seizure in the indomethacin group was reduced dramatically in all brain areas. We conclude that 1) bicuculline-induced seizures result in pial arteriolar dilation and increased CBF; 2) CSF levels of prostanoids increase during seizures; and 3) pretreatment with indomethacin severely blunts increases in CBF during seizures.
Regional venous outflow, blood volume, and sympathetic nerve activity during severe hypoxia
Authors: Hoka S. , Bosnjak Z. J. , Arimura H. , Kampine J. P.
Published: December 2017

We examined the dynamic changes in venous outflow from the splanchnic, coronary, and remaining other vascular beds and changes in systemic blood volume (SBV) in response to severe hypoxia (PO2 = 17 mmHg) in dogs using cardiopulmonary bypass and a reservoir. Splanchnic venous outflow, which also includes renal outflow in this study, decreased by 40%, and coronary venous outflow increased by 400% at 3.5 min after initiating severe hypoxia. Severe hypoxia caused a marked decrease in SBV of 23 +/- 1 and 9 +/- 2 ml/kg in spleen-intact and splenectomized dogs, respectively. The decrease in SBV was attenuated by 60 (P less than 0.01) and 83% (P less than 0.01) after the carotid and aortic chemoreceptor denervation (which was accompanied by baroreceptor denervation) and after hexamethonium infusion (10 mg/kg), respectively. Sympathetic efferent nerve activity revealed a tremendous augmentation, which began to rise at a PO2 of 40 mmHg before chemoreceptor denervation and at a PO2 of 22 mmHg after denervation. These results show that severe hypoxia causes a marked decrease in SBV, 60% of which is caused by active splenic contraction, and suggest that the sympathetic efferent nerve activity, which is augmented by the stimulation of chemoreceptors as well as the central nervous system, contributes greatly to those hypoxic changes.
Developmental regulation of cardiac calcium channels and contractile sensitivity to [Ca]o
Authors: Marsh J. D. , Allen P. D.
Published: December 2017

To test the hypothesis that alterations in Ca-channel properties are a major factor in developmental changes in Ca sensitivity of the heart, we quantitated Ca-channel pharmacological properties during development of the chick heart and related pharmacological properties of Ca channels to the ability of channels to modulate contractility. Force-pCa curves were determined for chick hearts during development. From 3 to 5 days in ovo to 3-4 days posthatched, there was more than 1 log decrease in sensitivity to extracellular calcium concentration [( Ca]o) PN200-100 ligand-binding studies in cardiac membranes revealed no change in dissociation constant (KD; 660-1,040 pM; P = NS) during development, but between 18 days in ovo and 3-4 days posthatched, there was an increase in the number of binding sites from 2,180 +/- 260 to 3,530 +/- 410 fmol/mg (P less than 0.01). This change could not be attributed to nonspecific change in membrane composition. For intact ventricular strips, there was a developmental decrease in contractile sensitivity to the Ca-channel agonist BAY K 8644 despite the increase in Ca channels as identified by ligand binding. Thus abundance of dihydropyridine binding sites increases during chick ventricular development, but this is dissociated from the physiological response to a Ca-channel agonist.
Ischemia-induced and reperfusion-induced arrhythmias: importance of heart rate
Authors: Bernier M. , Curtis M. J. , Hearse D. J.
Published: December 2017

The relationship between heart rate and ischemia-induced and reperfusion-induced arrhythmias was studied using 573 isolated rat hearts. Hearts (12/group), subjected to 7 min of coronary occlusion and 10 min reperfusion, were paced at 300, 330, 360, 390, 420, 480, or 540 beats/min. Pacing either throughout the experiment or during ischemia alone led to a rate-dependent increase in the incidence of reperfusion-induced ventricular fibrillation (VF) from 25% in the unpaced hearts to greater than 90% when the rate was 420 beats/min or higher. However, pacing during reperfusion alone did not increase the incidence of reperfusion-induced VF. In separate hearts, the right atrium was removed to permit examination of both low and high rates (167 +/- 2, 240, 336 +/- 3, or 480 beats/min throughout the experiment) over a wide range of durations of occlusion (3, 5, 7, 10, 15, 20, or 40 min). Ischemia-induced VF incidence was critically dependent on heart rate, low rates being protective. During reperfusion, the incidence of VF was also highly rate dependent if reperfusion was initiated within 10 min of the onset of ischemia (ranging from 8% when rate was 167 +/- 2 beats/min to 100% when rate was 480 beats/min) but was unrelated to heart rate when reperfusion occurred at later times (ranging from 33 to 50% when ischemia duration was 40 min). Heart rate can therefore influence susceptibility to ischemia- and reperfusion-induced arrhythmias, probably as a result of an effect on the rate of development of ischemic injury.
Relation between phosphate metabolites and oxygen consumption of heart in vivo
Authors: Katz L. A. , Swain J. A. , Portman M. A. , Balaban R. S.
Published: December 2017

The relation between induced increases in cardiac work and phosphate metabolites was investigated in the canine heart in vivo to evaluate the role of ATP hydrolysis products, ADP and inorganic phosphate (Pi), in the control of myocardial oxygen consumption (MVO2). In these studies, myocardial blood flow and oxygen consumption were simultaneously measured with the 31P-nuclear magnetic resonance (NMR)-detected phosphate metabolites. Three protocols were used to increase myocardial work: pacing, epinephrine, and phenylephrine infusions. When these protocols were used, no or only slight changes in myocardial ATP, Pi, and creatine phosphate were observed with a greater than threefold increase in MVO2. The calculated intracellular free Mg concentration, ADP, and pH were also only slightly affected by these increases in work. These data indicate that a simple model involving the feedback of cytosolic ADP and Pi to the mitochondria regulating respiration is inadequate to explain respiratory control in vivo. These data suggest that some other parameters or cooperativity effects involving the phosphate metabolites must play a role in the feedback between respiration and work in the heart in vivo.
Measurement of osmotic reflection coefficient for small molecules in cat hindlimbs
Authors: Wolf M. B. , Watson P. D.
Published: December 2017

Capillary osmotic reflection coefficients (sigma) for NaCl, urea, sucrose, and raffinose were measured in the isolated, perfused cat hindlimb using the osmotic transient technique. sigma were determined from the ratio of the maximum rate of transcapillary absorption [delta Jv(max)] to the increase in the osmotic pressure (25-35 mosmol/kg H2O) in the arterial inflow (delta pi a) produced by adding one of the molecules to an albumin-electrolyte perfusate containing isoproterenol (greater than 10(-7) M). delta Jv (max) was determined from organ weight and delta pi a from perfusate osmolalities. For each molecule, the delta Jv(max)/delta pi a ratio increased monotonically with perfusate flow rates (Q) to Q greater than 100 ml.min-1.100 g-1. This ratio was independent of the size of the delta pi a. Apparent sigma values were calculated by dividing these ratios by the capillary hydraulic capacity determined in other studies. At low Q, apparent sigma was comparable to the approximately 0.1 values found by others in skeletal muscle. At the highest Q, apparent sigma for these molecules were at least 0.5. These data are consistent with at least 50% of transcapillary water flow moving through a water-exclusive pathway.
Depression of heart sarcolemmal Ca2+-pump activity by oxygen free radicals
Authors: Kaneko M. , Beamish R. E. , Dhalla N. S.
Published: December 2017

Although oxygen free radicals have been implicated as mediators of cellular injury in myocardial ischemia-reperfusion, the exact nature of defects produced by these radicals is not clear. Because sarcolemmal Ca2+-pump is involved in the efflux of Ca2+ from the cell, this study was undertaken to examine the effects of oxygen free radicals on sarcolemmal ATP-dependent Ca2+ accumulation and Ca2+-stimulated Mg2+-dependent adenosinetriphosphatase (ATPase) activities as well as lipid peroxidation of membrane phospholipids. Isolated rat heart sarcolemmal membranes were incubated with xanthine + xanthine oxidase [a superoxide anion radical (O2-)-generating system], H2O2, or H2O2 + Fe2+ [a hydroxyl radical (HO.)-generating system] and assayed for Ca2+-pump activities. O2- inhibited the Ca2+-pump activities in a time-dependent manner; a significant inhibition of Ca2+-stimulated ATPase activity was seen after 1 min of incubation. Superoxide dismutase showed a protective effect on depression in Ca2+-pump activities caused by O2-.H2O2 inhibited Ca2+-pump activities in a dose-dependent manner; this inhibition was protected by the addition of catalase. HO. depressed the Ca2+-pump activities to a greater extent in comparison with H2O2. Mannitol showed a protective effect on HO.-induced inhibition of Ca2+-pump activities. The promotion of lipid peroxidation by free radicals was evident from increased formation of malondialdehyde. These results indicate that the sarcolemmal membrane is altered on exposure to oxygen free radicals, and this may result in depressing the Ca2+-pump mechanism for Ca2+ efflux from the myocardial cell.
Erythrocytes decrease myocardial hydrogen peroxide levels and reperfusion injury
Authors: Brown J. M. , Grosso M. A. , Terada L. S. , Beehler C. J. , Toth K. M. , Whitman G. J. , Harken A. H. , Repine J. E.
Published: December 2017

Reperfusion with untreated, carbon monoxide-treated, or glutaraldehyde-fixed human erythrocytes (RBC) increased ventricular function and decreased myocardial hydrogen peroxide (H2O2) levels [assessed by H2O2-dependent aminotriazole (AMT) inactivation of myocardial catalase activities] of ischemic, isolated rat hearts. In contrast, reperfusion with RBC that lacked catalase (AMT treated) and/or glutathione (N-ethylmaleimide treated) did not increase ventricular function or decrease myocardial H2O2 levels as much as reperfusion with untreated RBC. By comparison, reperfusion with superoxide dismutase-depleted (diethyldithiocarbamate-treated) or anion channel-inhibited (diisothiocyanodisulfonic acid stilbene-treated) RBC increased ventricular function and decreased myocardial H2O2 levels the same as untreated RBC. The results suggest that catalase and/or glutathione in intact RBC can decrease endogenously generated H2O2 and related reperfusion injury in ischemic, isolated perfused hearts.
Impairment of endothelium-dependent dilatation of cerebral arterioles during diabetes mellitus
Authors: Mayhan W. G.
Published: December 2017

The goal of this study was to determine whether responses of cerebral arterioles to vasoactive substances released by platelets are altered during diabetes mellitus. To induce diabetes, rats were injected with streptozotocin (50-60 mg/kg ip). Rats were characterized as diabetic by a blood glucose of greater than 300 mg/dl. Diameter of pial arterioles was measured during superfusion with ADP, serotonin, and the thromboxane analogue (U-46619), with the use of intravital microscopy in control (non-diabetic) and diabetic rats. ADP (10(-5)M) increased pial arteriolar diameter by 13 +/- 1% (mean +/- SE) in control rats and did not change diameter of arterioles in diabetic rats (1 +/- 1%). Serotonin (10(-5)M) increased diameter of cerebral arterioles by 9 +/- 1% in control rats and constricted arterioles by 5 +/- 2% in diabetic rats. Nitroglycerin produced similar dilatation of cerebral arterioles in control and diabetic rats, suggesting that impaired dilatation of cerebral arterioles in diabetic rats was not related to nonspecific impairment of vasodilatation. The thromboxane analogue U-46619 produced similar constriction of cerebral arterioles in control and diabetic rats. Thus endothelium-dependent dilatation of cerebral arterioles in response to ADP and serotonin is profoundly impaired in diabetic rats.
Length-tension relationship of vascular smooth muscle in single arterioles
Authors: Davis M. J. , Gore R. W.
Published: December 2017

Longitudinal response gradients in the microcirculation may in part be explained in terms of the length-tension relationship of vascular smooth muscle at different points along the vascular tree. To test this hypothesis, four branching orders of arterial vessels (20-80 microns ID) were dissected from the hamster cheek pouch and cannulated with concentric micropipettes. Intraluminal pressure was monitored with a servo-null micropipette, and arteriolar dimensions were measured using a videomicrometer. All arterioles developed spontaneous tone in physiological saline solution. Pressure-diameter curves were recorded for maximally activated vessels and for passive vessels. Maximal active wall tension varied nearly threefold, but maximal active medial wall stress (approximately 4 x 10(6) dyn/cm2) varied only approximately 20% between the different vessel orders. These data support the concept that smooth muscle cells from vessels of different sizes are mechanically similar but do not completely explain the longitudinal response gradients reported in the cheek pouch microcirculation. An analysis of the effect of arteriolar wall buckling suggests that the luminal folds that develop at short vessel radii may broaden the peak of the active stress-length curve and extend the pressure range over which arterioles are most sensitive to physical and chemical stimuli.
Basal metabolic energy requirements of polarized and depolarized arrest in rat heart
Authors: Sternbergh W. C. , Brunsting L. A. , Abd-Elfattah A. S. , Wechsler A. S.
Published: December 2017

Basal energy requirements of polarized [tetrodotoxin (TTX), 25 microns] and depolarized [potassium (K), 20 mM] arrested hearts were studied by continuously measuring myocardial oxygen consumption (MVO2) during 60 min of normothermic arrest in isolated Langendorff-perfused rat hearts. TTX, a fast sodium channel blocker, was used to produce polarized arrest because of its specificity and reversibility. MVO2 was significantly lower in the polarized (TTX) group at all time points, a typical difference occurring 30 min after arrest (0.070 +/- 0.005 vs. 0.109 +/- 0.006 ml O2.min-1.g dry wt-1, P less than 0.001). Coronary flow was lower in the polarized group (14.3 +/- 1.4 vs. 28.4 +/- 2.2 ml.min-1.g dry wt-1, P less than 0.001, data at 30 min of arrest), but flow-restricted studies showed basal MVO2 to be independent of variation in coronary flow within this range. Recovery of function was similar in both groups. Ventricular pressure during cardiac arrest was lower in the polarized group (5.5 +/- 1.2 vs. 10.3 +/- 1.3 mmHg, P less than 0.01, data at 30 min of arrest), implying reduced myocardial wall tension and a lower intracellular calcium concentration. These results suggest that polarized arrest can decrease myocardial metabolic demands below that of depolarized arrest. A plausible mechanism is a reduction in myocardial wall tension caused by decreased calcium influx mediated by the Na-Ca exchanger.
Ventrolateral medullary lesions and fastigial cardiovascular response in beagles
Authors: Dormer K. J. , Person R. J. , Andrezik J. A. , Foreman R. D. , Braggio J. P.
Published: December 2017

These studies were designed to verify that the putative vasomotor center in the rostral ventrolateral medulla (RVLM) contained the outflow paths for the fastigial nucleus (FN) sympathoexcitatory cardiovascular response. If so, then lesions placed by radiofrequency heating (75 degrees C) or application of kainic acid (40 mM) pledgets would reduce or ablate the pressor-tachycardia response after electrical stimulation of FN. Anesthetized beagles (alpha-chloralose, 115 mg/kg) were used in this study to maintain consistency in medullary brain stem anatomy. A ventral brain stem approach exposed the three chemosensitive zones of Mitchell, Schlaefke, and Loeschcke. In other species the intermediate zone and a portion of the rostral zone underlie the Hokfelt C1 cell group and the putative RVLM vasomotor center. Heart rate, arterial and left ventricular (LV) pressures, and maximal rate of pressure development (LV dp/dt) increased 14-84% above control levels in response to stimulating FN 5-10 times the stimulation threshold. The cardiovascular response was abolished in four of six dogs that received bilateral radiofrequency lesions at a depth of 1-2 mm. In five of seven dogs that received kainate surface lesions, the response was substantially reduced but not abolished. These lesions were effective only in the RVLM, above the corresponding intermediate, but not adjacent rostral or caudal chemosensitive areas. The data support the hypotheses of others that an epinphrine-containing cell group in this region is a final common pathway of sympathoexcitation. Expression of the FN cardiovascular response is primarily mediated through this vasomotor region previously identified by others in the rat, cat, rabbit, and primate.(ABSTRACT TRUNCATED AT 250 WORDS)
Laser-Doppler assessment of brain microcirculation: effect of systemic alterations
Authors: Haberl R. L. , Heizer M. L. , Marmarou A. , Ellis E. F.
Published: December 2017

There is a need for new technical approaches whereby the cerebral microcirculation can be easily and continuously assessed. The objective of this study was to determine whether laser-Doppler (LD) flowmetry can be utilized to assess changes in cerebral cortical blood flow and to determine whether changes in blood perfusion measured by LD flowmetry correlate with simultaneously measured changes in flow measured by H2 clearance in cats or with changes in pial arteriolar diameter measured with a microscope in rabbits equipped with a closed cranial window. In the rabbit experiments a 0.84-mm-diam LD probe was inserted through a cranial window port, and in the cat experiments the probe was fixed adjacent to the H2 probe. The probe was fixed at a distance of 1-2 mm from the cortical surface, where it and its associated electronics detect changes in blood cell velocity and blood volume within a tissue volume of approximately 1 mm3. Volume and velocity are multiplied to provide a flow signal. When cerebral blood flow in cats was decreased by hyperventilation-induced hypocapnia and increased by norepinephrine-induced hypertension, the percent changes in LD flow and H2 clearance flow changed linearly (r = 0.94, slope = 0.97). When arterial PCO2 was increased from 28 to 48 mmHg in the rabbit experiments, the pial arterioles dilated 19 +/- 4% (mean +/- SE) and LD flow increased by 74 +/- 9%, LD flow changes which would be predicted by a third power relationship of diameter to flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Minor preload dependence of O2 consumption of unloaded contraction in dog heart
Authors: Yasumura Y. , Nozawa T. , Futaki S. , Tanaka N. , Suga H.
Published: December 2017

We studied whether end-diastolic volume (EDV) would affect myocardial oxygen consumption (VO2) of mechanically unloaded contraction in the cross-circulated dog heart, as expected from the concept of the myocardial length-dependent activation. We made preloaded but maximally unloaded contractions from different EDVs by quickly releasing ventricular volume to eliminate systolic pressure development and hence to minimize the VO2 for mechanical load during the contraction. We then studied the relation between VO2 and EDV. The VO2 of the almost unloaded contraction from a relatively large EDV slightly exceeded the VO2 of the isovolumic contraction at V0, where V0 is the volume at which peak isovolumic pressure was zero. However, the excess VO2 could be ascribed to the residual systolic pressure-volume area (PVA) adversely produced from the large EDV, where PVA is a measure of the total mechanical energy generated during contraction. Therefore, we considered that VO2 was practically little dependent on EDV. We interpreted this finding as an indication that an increase, if any, in VO2 due to the length-dependent activation of the excitation-contraction coupling was practically negligible in the whole heart preparation.
Rate of activation of renin-angiotensin-aldosterone axis and sodium intake in rats
Authors: Holtzman E. , Braley L. M. , Menachery A. , Williams G. H. , Hollenberg N. K.
Published: December 2017

When sodium intake in the rat is reduced abruptly from the typical high level to a very low level (0.02%), sodium excretion falls exponentially, with a half time of 2-3 h. The result is that the rat achieves external sodium balance, in which intake equals excretion, on the new low intake within a few hours. In this study, we assessed the rate of activation of the renin-angiotensin-aldosterone axis and its contribution to blood pressure during that interval. Plasma renin activity and angiotensin II concentration had risen sharply within 8 h and did not change over the next 40 h. Plasma aldosterone concentration, on the other hand, continued to rise over 48 h. Within 8 h, blood pressure dependency on angiotensin II had increased sharply, as assessed by depressor responses to an angiotensin antagonist (Sar1-Ala8-angiotensin II) and to converting-enzyme inhibition (captopril). The depressor response to neither agent changed over the next 40 h. The pressor response to angiotensin II was blunted significantly by 8 h and also did not change over the next 40 h. The findings indicate that the rapid tempo of sodium homeostasis in the rat is matched by an equally rapid tempo of activation of the renin-angiotensin system, although the factors responsible for aldosterone release are probably more complex. Experiments to assess the renin-angiotensin system in the rat must be designed with this rapid tempo in mind.
Right ventricular performance after monocrotaline-induced pulmonary hypertension
Authors: Werchan P. M. , Summer W. R. , Gerdes A. M. , McDonough K. H.
Published: December 2017

Chronic pulmonary hypertension leads to a compensatory hypertrophy of the right ventricle (RV). Performance of the hypertrophied heart has been shown to vary depending on the type and severity of the overload, the species, age, and sex of the animal in which the hypertrophy is induced and the ventricle to which the overload is applied (left ventricle vs. right ventricle). In this study we employed two novel approaches to examine the performance of the hypertrophied right ventricle in male Sprague-Dawley rats. First, monocrotaline (MCT), a pyrrolizidine alkaloid isolated from the plant Crotalaria spectabilis, was used to noninvasively induce chronic pulmonary hypertension, RV pressure overload, and RV hypertrophy. After 5 wk the RV-to-(left ventricle + septum) ratio was increased by 94% over control. The volume of isolated right ventricular myocytes from MCT-treated rats was increased due primarily to an increase in cell cross-sectional area. Second, a stable, isolated, working heart preparation, normally used to study left ventricular function, was modified to study right ventricular function. In vitro ventricular performance of severely hypertrophied hearts was elevated compared with control hearts at all preloads. Significant elevations in positive and negative maximum pressure development (dP/dtmax) suggested that both the rate of pressure development and the rate of relaxation were enhanced. Coronary flow and RV-diastolic pressure were similar in the MCT and control group. Thus RV hypertrophy caused by a chronic pressure overload induced by MCT resulted in enhanced ventricular performance with no evidence of failure.
Anti-EDRF effect of tumor necrosis factor in isolated, perfused cat carotid arteries
Authors: Aoki N. , Siegfried M. , Lefer A. M.
Published: December 2017

Cat carotid arteries that have an intact endothelium were isolated and perfused with Krebs-Henseleit solution containing recombinant human tumor necrosis factor (rhTNF). Perfused arteries were preconstricted with KCl and then dilated with acetylcholine (ACh) or acidified NaNO2. After perfusion with TNF (4 micrograms/ml) for 120 min, the ACh-induced vasodilator response was markedly blunted, but the NaNO2 vasodilator response was not significantly affected. Arteries perfused with 2 micrograms/ml TNF for 60-120 min or with 4 micrograms/ml for 60 min did not develop a significantly impaired relaxation to ACh. Moreover, perfusion with 20-100 micrograms/ml cycloheximide, an inhibitor of protein synthesis, blocked the TNF-induced impairment of the relaxation to ACh. On the other hand, the vasodilator response to acidified NaNO2 did not change in any perfused carotid arteries. These results suggest that TNF promotes the synthesis of proteins that contribute to the damage of endothelial cells directly, probably by inhibiting endothelium-derived relaxing factor release.
Increased lymphatic elimination of interstitial hyaluronan during E. coli sepsis in sheep
Authors: Lebel L. , Smith L. , Risberg B. , Laurent T. C. , Gerdin B.
Published: December 2017

The effect of septicemia on the elimination of hyaluronan (HA) from the lung interstitium was investigated in awake sheep with chronic lung lymph and thoracic duct fistulas. The result was compared with that after elevation of left atrial pressure (LAP). Lymph was sampled before and after a 20-min infusion of Escherichia coli (10(9) bacteria/kg body wt.), after elevation of LAP, or both. Infusion of E. coli caused an increased flux of HA in lung lymph and thoracic duct lymph. After an elevation of LAP, the HA flux in lung lymph was increased to a comparable extent. In animals subjected to an increase in LAP and subsequently to infusion of E. coli, no additive effect on HA flux was seen. The weight-average molecular weight of HA in lung lymph was increased both after sepsis and after elevation of LAP. The findings show that sepsis and elevated transvascular hydrostatic pressure result in increased mobilization of HA from the interstitium. This might partly explain the increased HA concentrations in plasma in clinical sepsis and may also lead to a change in the characteristics of the interstitial matrix in this condition.
The mutual interaction of vasoconstriction and endothelial damage in stenotic arteries
Authors: Tulenko T. N. , Constantinescu D. , Kikuchi T. , Cox R. H. , Santamore W. P.
Published: December 2017

Page H885: T. N. Tulenko, D. Constantinescu, T. Kikuchi, R. H. Cox, and W. P. Santamore. “The mutual interaction of vasoconstriction and endothelial damage in stenotic arteries.” Figure 5 should appear as the following.

(See PDF)
Effect of circulating vasopressin on arterial pressure regulation in rats
Authors: Pawloski C. M. , Eicker N. M. , Ball L. M. , Mangiapane M. L. , Fink G. D.
Published: December 2017

It has been hypothesized that moderately increased blood levels of arginine vasopressin (AVP) contribute to the development and/or maintenance of hypertension. In this study, male Sprague-Dawley rats on a fixed 1 meq daily sodium intake received 10-day intravenous infusions of 0.2 and 2.0 ng.kg-1.min-1 AVP. The higher infusion rate was above the acute vasoconstrictor threshold for AVP administration and also produced a maximal antidiuretic effect. During chronic AVP administration, however, daily mean arterial pressure, heart rate, and body fluid composition were not changed, despite a maintained antidiuresis. To test the hypothesis that circulating AVP failed to cause hypertension as a result of sensitization of the baroreflex or a direct sympathoinhibitory effect of the peptide, additional experiments were performed in rats subjected to sinoaortic denervation (SAD) or ablation of the area postrema (APX). Infusion of AVP for 10 days into SAD or APX rats caused a sustained antidiuresis but did not change arterial pressure, heart rate, or body fluid composition. In all groups of rats, the depressor response to ganglionic blockade (20 mg/kg hexamethonium) was used to estimate the autonomic component of resting arterial pressure; no change in autonomic cardiovascular control was found using this method in any of the groups during AVP infusion. Long-term elevation of plasma AVP in rats, therefore, does not cause hypertension or significantly affect autonomic regulation of arterial pressure.