The venous circulation: a piscine perspective.

Vascular capacitance describes the pressure-volume relationship of the circulatory system. The venous vasculature, which is the main capacitive region in the circulation, is actively controlled by various neurohumoral systems. In terrestrial animals, vascular capacitance control is crucial to prevent orthostatic blood pooling in dependent limbs, while in aquatic animals like fish, the effects of gravity are cancelled out by hydrostatic forces making orthostatic blood pooling an unlikely concern for these animals. Nevertheless, changes in venous capacitance have important implications on cardiovascular homeostasis in fish since it affects venous return and cardiac filling pressure (i.e. central venous blood pressure), which in turn may affect cardiac output. The mean circulatory filling pressure is used to estimate vascular capacitance. In unanaesthetized animals, it is measured as the central venous plateau pressure during a transient stoppage of cardiac output. So far, most studies of venous function in fish have addressed the situation in teleosts (notably the rainbow trout, Oncorhynchus mykiss), while any information on elasmobranchs, cyclostomes and air-breathing fishes is more limited. This review describes venous haemodynamic concepts and neurohumoral control systems in fish. Particular emphasis is placed on venous responses to natural cardiovascular challenges such as exercise, environmental hypoxia and temperature changes.     

Reflex control of vascular capacitance during hypoxia, hypercapnia, or hypoxic hypercapnia

We tested the hypothesis that the changes in venous tone induced by changes in arterial blood oxygen or carbon dioxide require intact cardiovascular reflexes. Mongrel dogs were anesthetized with sodium pentobarbital and paralyzed with veruronium bromide. Cardiac output and central blood volume were measured by indocyanine green dilution. Mean circulatory filling pressure, an index of venous tone at constant blood volume, was estimated from the central venous pressure during transient electrical fibrillation of the heart. With intact reflexes, hypoxia (arterial PaO2 = 38 mmHg), hypercapnia (PaCO2 = 72 mmHg), or hypoxic hypercapnia (PaO2 = 41; PaCO2 = 69 mmHg) (1 mmHg = 133.32 Pa) significantly increased the mean circulatory filling pressure and cardiac output. Hypoxia, but not normoxic hypercapnia, increased the mean systemic arterial pressure and maintained the control level of total peripheral resistance. With reflexes blocked with hexamethonium and atropine, systemic arterial pressure supported with a constant infusion of norepinephrine, and the mean circulatory filling pressure restored toward control with 5 mL/kg blood, each experimental gas mixture caused a decrease in total peripheral resistance and arterial pressure, while the mean circulatory filling pressure and cardiac output were unchanged or increased slightly. We conclude that hypoxia, hypercapnia, and hypoxic hypercapnia have little direct influence on vascular capacitance, but with reflexes intact, there is a significant reflex increase in mean circulatory filling pressure.     

Role of beta-adrenergic agonists in the control of vascular capacitance

The role of beta-adrenergic agonists, such as isoproterenol, on vascular capacitance is unclear. Some investigators have suggested that isoproterenol causes a net transfer of blood to the chest from the splanchnic bed. We tested this hypothesis in dogs by measuring liver thickness, cardiac output, cardiopulmonary blood volume, mean circulatory filling pressure, portal venous, central venous, pulmonary arterial, and systemic arterial pressures while infusing norepinephrine (2.6 micrograms.min-1.kg-1), or isoproterenol (2.0 micrograms.min-1.kg-1), or histamine (4 micrograms.min-1.kg-1), or a combination of histamine and isoproterenol. Norepinephrine (an alpha- and beta 1-adrenergic agonist) decreased hepatic thickness and increased mean circulatory filling pressure, cardiac output, cardiopulmonary blood volume, total peripheral resistance, and systemic arterial and portal pressures. Isoproterenol increased cardiac output and decreased total peripheral resistance, but it had little effect on liver thickness or mean circulatory filling pressure and did not increase the cardiopulmonary blood volume or central venous pressure. Histamine caused a marked increase in portal pressure and liver thickness and decreased cardiac output, but it had little effect on the estimated mean circulatory filling pressure. Isoproterenol during histamine infusions reduced histamine-induced portal hypertension, reduced liver size, and increased cardiac output. We conclude that the beta-adrenergic agonist, isoproterenol, has little influence on vascular capacitance or liver volume of dogs, unless the hepatic outflow resistance is elevated by agents such as histamine.     

Venous hemodynamic responses to acute temperature increase in the rainbow trout (Oncorhynchus mykiss)

Many ectotherms regularly experience considerable short-term variations in environmental temperature, which affects their body temperature. Here we investigate the cardiovascular responses to a stepwise acute temperature increase from 10 to 13 and 16 degrees C in rainbow trout (Oncorhynchus mykiss). Cardiac output increased by 20 and 31% at 13 and 16 degrees C, respectively. This increase was entirely mediated by an increased heart rate (fH), whereas stroke volume (SV) decreased significantly by 20% at 16 degrees C. The mean circulatory filling pressure (MCFP), a measure of venous capacitance, increased with temperature. Central venous pressure (Pven) did not change, whereas the pressure gradient for venous return (MCFP-Pven) was significantly increased at both 13 and 16 degrees C. Blood volume, as measured by the dilution of 51Cr-labeled red blood cells, was temperature insensitive in both intact and splenectomized trout. This study demonstrates that venous capacitance in trout decreases, but cardiac filling pressure as estimated by Pven does not change when cardiac output increases during an acute temperature increase. SV was compromised as fH increased with temperature. The decreased capacitance likely serves to prevent passive pooling of blood in the venous periphery and to maintain cardiac filling pressure and a favorable pressure gradient for venous return.     

Effects of freshwater and saltwater adaptation and dietary salt on fluid compartments, blood pressure, and venous capacitance in trout

Trout are of interest in defining the relationship between fluid and salt balance on cardiovascular function because they thrive in freshwater (FW; volume loading, salt depleting), saltwater (SW; volume depleting, salt loading), and FW while fed a high-salt diet (FW-HS; volume and salt loading). The effects of chronic (>2 wk) adaptation to these three protocols on blood volume (51Cr red cell space), extracellular fluid volume (99mTc-diethylene triaminepenta-acetic acid space), arterial (dorsal aortic; P(DA)) and venous (ductus Cuvier; Pven) blood pressure, mean circulatory filling pressure (zero-flow Pven), and vascular capacitance were examined in the present study on unanesthetized rainbow trout. Blood volume, extracellular fluid volume, P(DA), Pven, and mean circulatory filling pressure progressively increased in the order SW < FW < FW-HS. Vascular capacitance in SW fish appeared to be continuous with the capacitance curve of FW fish and reflect a passive volume-dependent unloading of the venous system of FW fish. Vascular capacitance curves for FW-HS fish were displaced upward and parallel to those of FW fish, indicative of an active increase in unstressed blood volume without any change in vascular compliance. These studies are the first in any vertebrate to measure the relationship between fluid compartments and cardiovascular function during independent manipulation of volume and salt balance, and they show that volume, but not salt, balance is the primary determinant of blood pressure in trout. They also present a new paradigm with which to investigate the relative contributions of water and salt balance in cardiovascular homeostasis.     

Effects of nifedipine and captopril on vascular capacitance of ganglion-blocked anesthetized dogs

The hemodynamic effects of nifedipine and captopril at doses producing similar reductions in arterial pressure were studied in pentobarbital-anesthetized ventilated dogs after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline circulating blood volumes and after increases of 5 and 10 mL/kg. Central blood volumes (pulmonary artery to aortic root) were determined from transit times, and separately determined cardiac outputs (right atrium to pulmonary artery) were estimated by thermodilution. Nifedipine (n = 5) increased Pmcf at all circulating blood volumes and reduced total vascular capacitance without a change in total vascular compliance. Central blood volume, right atrial pressure, and cardiac output were increased with induced increases in circulating blood volume. In contrast, captopril (n = 5) did not alter total vascular capacitance, central blood volume, right atrial pressure, or cardiac output at baseline or with increased circulating volume. Thus, at doses producing similar reductions in arterial pressure, nifedipine but not captopril increased venous return and cardiac output in ganglion-blocked dogs.     

Adrenergic control of venous capacitance during moderate hypoxia in the rainbow trout (Oncorhynchus mykiss): role of neural and circulating catecholamines

Central venous blood pressure (P(ven)) increases in response to hypoxia in rainbow trout (Oncorhynchus mykiss), but details on the control mechanisms of the venous vasculature during hypoxia have not been studied in fish. Basic cardiovascular variables including P(ven), dorsal aortic blood pressure, cardiac output, and heart rate were monitored in vivo during normoxia and moderate hypoxia (P(W)O(2) = approximately 9 kPa), where P(W)O(2) is water oxygen partial pressure. Venous capacitance curves for normoxia and hypoxia were constructed at 80-100, 90-110, and 100-120% of total blood volume by transiently (8 s) occluding the ventral aorta and measure P(ven) during circulatory arrest to estimate the mean circulatory filling pressure (MCFP). This allowed for estimates of hypoxia-induced changes in unstressed blood volume (USBV) and venous compliance. MCFP increased due to a decreased USBV at all blood volumes during hypoxia. These venous responses were blocked by alpha-adrenoceptor blockade with prazosin (1 mg/kg body mass). MCFP still increased during hypoxia after pretreatment with the adrenergic nerve-blocking agent bretylium (10 mg/kg body mass), but the decrease in USBV only persisted at 80-100% blood volume, whereas vascular capacitance decreased significantly at 90-110% blood volume. In all treatments, hypoxia typically reduced heart rate while cardiac output was maintained through a compensatory increase in stroke volume. Despite the markedly reduced response in venous capacitance after adrenergic blockade, P(ven) always increased in response to hypoxia. This study reveals that venous capacitance in rainbow trout is actively modulated in response to hypoxia by an alpha-adrenergic mechanism with both humoral and neural components.     

Effects of leg venous hemodynamics on cardiovascular responses to lower body negative pressure and aging

In aged people, decreases in stroke volume and cardiac output during orthostatic challenge are less. It is suggested that the stiffness of blood vessels is greater in the elderly, blunting leg venous pooling and drop in central blood volume in an upright position. Leg venous hemodynamics plays an important role in human cardiovascular homeostasis against gravitational stress. This study aimed to clarify how aging influences the leg venous hemodynamics and its contribution to cardiovascular homeostasis during lower body negative pressure (LBNP) in humans.     

Enforced exercise, but not acute temperature elevation, decreases venous capacitance in the stenothermal Antarctic fish Pagothenia borchgrevinki

The venous haemodynamic response to enforced exercise and acute temperature increase was examined in the Antarctic fish Pagothenia borchgrevinki (borch) to enable comparisons with the existing literature for temperate species, and investigate if the unusual cardiovascular response to temperature changes previously observed in the borch can be linked to an inability to regulate the venous vasculature. Routine central venous blood pressure (P (cv)) was 0.08 kPa and the mean circulatory filling pressure (P (mcf); an index of venous capacitance) was 0.14 kPa. Acute warming from 0 to 2.5 and 5 degrees C increased heart rate (f (H)), while dorsal aortic blood pressure (P (da)) decreased. P (mcf) did not change, while P (cv) decreased significantly at 5 degrees C. This contrasts with the venoconstriction previously observed in rainbow trout in response to increased temperature. Exercise resulted in small increases in P (mcf) and P (cv), a response that was abolished by alpha-adrenoceptor blockade. This study demonstrates that the heart of P. borchgrevinki normally operates at positive filling pressures (i.e. P (cv)) and that venous capacitance can be actively regulated by an alpha-adrenergic mechanism. The lack of decrease in venous capacitance during warming may suggest that a small increase in venous tone is offset by a passive temperature-mediated increase in compliance.     

Cardiovascular response to acute hypovolemia in relation to age. Implications for orthostasis and hemorrhage

Venous compliance in the legs of aging man has been found to be reduced with decreased blood pooling (capacitance response) in dependent regions, and this might lead to misinterpretations of age-related changes in baroreceptor function during orthostasis. The hemodynamic response to hypovolemic circulatory stress was studied with the aid of lower-body negative pressure (LBNP) of 60 cmH(2)O in 33 healthy men [18 young (mean age 22 yr) and 15 old (mean age 65 yr)]. Volumetric technique was used in the study of capacitance responses in the calf and arm as well as transcapillary fluid absorption in the arm. LBNP led to smaller increase in heart rate (P < 0.001) and peripheral resistance (P < 0.01) and reduced transcapillary fluid absorption in the arm (P < 0.05) in old subjects. However, blood pooling in the calf was reduced in old subjects (1.66 +/- 0.10 vs. 2.17 +/- 0.13 ml/100 ml tissue; P < 0. 01). Accordingly, during similar blood pooling in the calf (LBNP 80 cmH(2)O in old subjects), no changes in cardiovascular reflex responses with age were found. The capacitance response in the arm (mobilization of peripheral blood to the central circulation) was still reduced, however (0.67 +/- 0.10 vs. 1.37 +/- 0.11 ml/100 ml tissue; P < 0.01). Thus the reduced cardiovascular reflex response found in the elderly during orthostatic stress seems to be caused by a reduced capacitance response in the legs with age and a concomitant smaller central hypovolemic stimulus rather than a reduced efficiency of the reflex response. With similar hypovolemic circulatory stress, no changes in cardiovascular reflex responses are seen with age. The capacitance response in the arm (mobilization of peripheral blood toward the central circulation) is reduced, however, by approximately 50% in the elderly. This might seriously impede the possibility of survival of an acute blood loss.     

Influence of pregnancy on mean systemic filling pressure and the cardiac function curve in guinea pigs.

To assess the degree of circulatory fullness and to evaluate the influence of peripheral and cardiac factors in the regulation of cardiac output during pregnancy, the following studies were conducted using pentobarbital-anesthetized, open-chest nonpregnant and late term pregnant guinea pigs. Mean circulatory filling pressure was taken as the equilibrium pressure when the pulmonary artery was constricted. Total vascular compliance was assessed by +/- 5-mL changes in blood volume performed while this constriction was maintained. A separate group of guinea pigs was prepared with a pulmonary artery electromagnetic flow probe and right atrial catheter. Rapid infusion of saline was used to increase right atrial pressure while the cardiac output was determined. Pregnancy was characterized by the following changes relative to nonpregnant controls: 51Cr-labelled RBC blood volume increased from 55 +/- 3 to 67 +/- 3 mL/kg; mean circulatory filling pressure increased from 7.1 +/- 0.2 to 8.0 +/- 0.5 mmHg (1 mmHg = 133.322 Pa); right atrial pressure decreased from 3.4 +/- 0.2 to 2.1 +/- 0.3 mmHg; and cardiac output increased from 71.8 +/- 3.9 to 96.8 +/- 3.3 mL.min-1.kg-1. Total vascular compliance was not changed (2.1 +/- 0.1 mL.kg-1.mmHg-1) and most of the expanded blood volume was accommodated as unstressed volume. The cardiac function curve was shifted upwards in pregnant animals. The resistance to venous return, as determined from the slope of the venous return curves, was not changed. These data suggest that the circulation of the pregnant guinea pig is slightly overfilled.(ABSTRACT TRUNCATED AT 250 WORDS)     

Central venous pressure and mean circulatory filling pressure in the dogfish Squalus acanthias: adrenergic control and role of the pericardium

Subambient central venous pressure (Pven) and modulation of venous return through cardiac suction (vis a fronte) characterizes the venous circulation in sharks. Venous capacitance was estimated in the dogfish Squalus acanthias by measuring the mean circulatory filling pressure (MCFP) during transient occlusion of cardiac outflow. We tested the hypothesis that venous return and cardiac preload can be altered additionally through adrenergic changes of venous capacitance. The experiments involved the surgical opening of the pericardium to place a perivascular occluder around the conus arteriosus. Another control group was identically instrumented, but lacked the occluder, and was subjected to the same pharmacological protocol to evaluate how pericardioectomy affected cardiovascular status. Routine Pven was negative (-0.08+/-0.02 kPa) in control fish but positive (0.09+/-0.01 kPa) in the pericardioectomized group. Injections of 5 microg/kg body mass (Mb) of epinephrine and phenylephrine (100 microg/kg Mb) increased Pven and MCFP, whereas isoproterenol (1 microg/kg Mb) decreased both variables. Thus, constriction and relaxation of the venous vasculature were mediated through the respective stimulation of alpha- and beta-adrenergic receptors. Alpha-adrenergic blockade with prazosin (1 mg/kg Mb) attenuated the responses to phenylephrine and decreased resting Pven in pericardioectomized animals. Our results provide convincing evidence for adrenergic control of the venous vasculature in elasmobranchs, although the pericardium is clearly an important component in the modulation of venous function. Thus active changes in venous capacitance have previously been underestimated as an important means of modulating venous return and cardiac performance in this group.     

Venous responses during exercise in rainbow trout, Oncorhynchus mykiss: alpha-adrenergic control and the antihypotensive function of the renin-angiotensin system

The role of the alpha-adrenergic system in the control of cardiac preload (central venous blood pressure; P(ven)) and venous capacitance during exercise was investigated in rainbow trout (Oncorhynchus mykiss). In addition, the antihypotensive effect of the renin-angiotesin system (RAS) was investigated during exercise after alpha-adrenoceptor blockade. Fish were subjected to a 20-min exercise challenge at 0.66 body lengths s(-1) (BL s(-1)) while P(ven), dorsal aortic blood pressure (P(da)) and relative cardiac output (Q) was recorded continuously. Heart rate (f(H)), cardiac stroke volume (SV) and total systemic resistance (R(sys)) were derived from these variables. The mean circulatory filling pressure (MCFP) was measured at rest and at the end of the exercise challenge, to investigate potential exercise-mediated changes in venous capacitance. The protocol was repeated after alpha-adrenoceptor blockade with prazosin (1 mg kg(-1)M(b)) and again after additional blockade of angiotensin converting enzyme (ACE) with enalapril (1 mg kg(-1)M(b)). In untreated fish, exercise was associated with a rapid (within approx. 1-2 min) and sustained increase in Q and P(ven) associated with a significant increase in MCFP (0.17+/-0.02 kPa at rest to 0.27+/-0.02 kPa at the end of exercise). Prazosin treatment did not block the exercise-mediated increase in MCFP (0.25+/-0.04 kPa to 0.33+/-0.04 kPa at the end of exercise), but delayed the other cardiovascular responses to swimming such that Q and P(ven) did not increase significantly until around 10-13 min of exercise, suggesting that an endogenous humoral control mechanism had been activated. Subsequent enalapril treatment revealed that these delayed responses were in fact due to activation of the RAS, because resting P(da) and R(sys) were decreased further and essentially all cardiovascular changes during exercise were abolished. This study shows that the alpha-adrenergic system normally plays an important role in the control of venous function during exercise in rainbow trout. It is also the first study to suggest that the RAS may be an important modulator of venous pressure and capacitance in fish.     

Circulatory function at sub-zero temperature: venous responses to catecholamines and angiotensin II in the Antarctic fish <Emphasis Type="Italic">Pagothenia borchgrevinki</Emphasis>

Catecholamines increase arterial pressure by increasing cardiac output (Q) and stroke volume (V _s), while angiotensin II (ang II) also increases vascular resistance (R _sys) in the Antarctic fish Pagothenia borchgrevinki. Adrenaline, phenylephrine and ang II (Asn¹, Val⁵) were injected into P. borchgrevinki. Cardiovascular variables, including central venous pressure (P _cv) and mean circulatory filling pressure (P _mcf; an index of venous capacitance), were recorded to investigate if venous vasoconstriction can explain the increased V _s and Q and the arterial pressor response in this species. Routine P _cv and P _mcf were 0.11 ± 0.01 and 0.18 ± 0.02 kPa, respectively. All of the drugs caused moderate increases in P _cv and P _mcf and the responses were attenuated after α-adrenergic blockade with prazosin. Although dorsal aortic pressure (P _da) also increased in response to all agonists, the mechanisms differed. Adrenaline caused sustained increases in V _s and Q, while R _sys only rose transiently. Ang II had a slower effect than adrenaline and increased both R _sys and Q, while phenylephrine only increased R _sys. This study demonstrates that P _cv is positive and controlled by an α-adrenergic mechanism in P. borchgrevinki. However, given the relatively small venous response to adrenaline it seems more likely that the increases in V _s and Q from this agonist are due to direct effects on the heart.     

The effects of hindlimb unweighting on the capacitance of rat small mesenteric veins.

Microgravity is associated with an impaired cardiac output response to orthostatic stress. Mesenteric veins are critical in modulating cardiac filling through venoconstriction. The purpose of this study was to determine the effects of simulated microgravity on the capacitance of rat mesenteric small veins. We constructed pressure-diameter relationships from vessels of 21-day hindlimb-unweighted (HLU) rats and control rats by changing the internal pressure and measuring the external diameter. Pressure-diameter relationships were obtained both before and after stimulation with norepinephrine (NE). The pressure-diameter curves of HLU vessels were shifted to larger diameters than control vessels. NE (10(-4) M) constricted veins from control animals such that the pressure-diameter relationship was significantly shifted downward (i.e., to smaller diameters at equal pressure). NE had no effect on vessels from HLU animals. These results indicate that, after HLU, unstressed vascular volume may be increased and can no longer decrease in response to sympathetic stimulation. This may partially underlie the mechanism leading to the exaggerated fall in cardiac output and stroke volume seen in astronauts during an orthostatic stress after exposure to microgravity.     

Static filling pressure in patients during induced ventricular fibrillation

The static pressure resulting after the cessation of flow is thought to reflect the filling of the cardiovascular system. In the past, static filling pressures or mean circulatory filling pressures have only been reported in experimental animals and in human corpses, respectively. We investigated arterial and central venous pressures in supine, anesthetized humans with longer fibrillation/defibrillation sequences (FDSs) during cardioverter/defibrillator implantation. In 82 patients, the average number of FDSs was 4 +/- 2 (mean +/- SD), and their duration was 13 +/- 2 s. In a total of 323 FDSs, arterial blood pressure decreased with a time constant of 2.9 +/- 1.0 s from 77.5 +/- 34.4 to 24.2 +/- 5.3 mmHg. Central venous pressure increased with a time constant of 3.6 +/- 1.3 s from 7.5 +/- 5.2 to 11.0 +/- 5.4 mmHg (36 points, 141 FDS). The average arteriocentral venous blood pressure difference remained at 13.2 +/- 6.2 mmHg. Although it slowly decreased, the pressure difference persisted even with FDSs lasting 20 s. Lack of true equilibrium pressure could possibly be due to a waterfall mechanism. However, waterfalls were identified neither between the left ventricle and large arteries nor at the level of the diaphragm in supine patients. We therefore suggest that static filling pressures/mean circulatory pressures can only be directly assessed if the time after termination of cardiac pumping is adequate, i.e., >20 s. For humans, such times are beyond ethical options.     

Cardiorespiratory responses of animals to passive orthostasis after intermittent hypoxia during head-down tilt

Cardiorespiratory responses induced by upright tilt before and after intermittent hypoxia during head-down tilt, were investigated in rabbits. Arterial blood pressure, heart rate, central venous pressure, transmural filling pressure of the heart (calculated as the product of esophageal and central venous pressure), breathing frequency, esophageal pressure were measured in supine (baseline), head-down and upright posture. Our results indicate a reduction in orthostatic responses in cardiovascular system after intermittent hypoxia.     

Left ventricular reflex control of venous return and systemic vascular capacitance in dogs

The reflex effects of left ventricular distension on venous return, vascular capacitance, vascular resistance, and sympathetic efferent nerve activity were examined in dogs anesthetized with sodium pentobarbital. In addition, the interaction of left ventricular distension and the carotid sinus baroreflex was examined. Vascular capacitance was assessed by measuring changes in systemic blood volume, using extracorporeal circulation with constant cardiac output and constant central venous pressure. Left ventricular distension produced by balloon inflation caused a transient biphasic change in venous return; an initial small increase was followed by a late relatively large decrease. Left ventricular distension increased systemic blood volume by 3.8 +/- 0.6 mL/kg and decreased systemic blood pressure by 27 +/- 2 mmHg (1 mmHg = 133.3 Pa) at an isolated carotid sinus pressure of 50 mmHg. These changes were accompanied by a simultaneous decrease in sympathetic efferent nerve activity. When the carotid sinus pressure was increased to 125 and 200 mmHg, these responses were attenuated. It is suggested that left ventricular mechanoreceptors and carotid baroreceptors contribute importantly to the control of venous return and vascular capacitance.     

Effects of endothelin-1 and homologous trout endothelin on cardiovascular function in rainbow trout

The cardiovascular effects of endothelin (ET)-1 and the recently sequenced homologous trout ET were examined in unanesthetized trout, and vascular capacitance curves were constructed to evaluate the responsiveness of the venous system to ET-1. A bolus dose of 667 pmol/kg ET-1 doubled ventral aortic pressure; produced a triphasic pressor-depressor-pressor response in dorsal aortic pressure (P(DA)); increased central venous pressure, gill resistance, and systemic resistance; and decreased cardiac output, heart rate, and stroke volume. These responses were dose dependent. Bolus injection of trout ET (333 or 1,000 pmol/kg) produced essentially identical, dose-dependent cardiovascular responses as ET-1. Dorsal aortic infusion of 1 and 3 pmol. kg(-1). min(-1) ET-1 and central venous infusion into the ductus Cuvier of 0.3 and 1 pmol. kg(-1). min(-1) produced similar dose-dependent cardiovascular responses, although the increase in P(DA) became monophasic. The heightened sensitivity to central venous infusion was presumably due to the more immediate exposure of the branchial vasculature to the peptide. Infusion of 1 pmol. kg(-1). min(-1) ET-1 decreased vascular compliance but had no effect on unstressed blood volume. These results show that ETs affect a variety of cardiovascular functions in trout and that branchial vascular resistance and venous compliance are especially sensitive. The multiplicity of effectors stimulated by ET suggests that this peptide was extensively integrated into cardiovascular function early on in vertebrate phylogeny.     

Reduced orthostatic tolerance following 4 h head-down tilt

The cardiovascular responses to a 10-min 1.22 rad (70 degrees) head-up tilt orthostatic tolerance test (OST) was observed in eight healthy men following each of a 5-min supine baseline (control), 4 h of 0.1 rad (6 degrees) head-down tilt (HDT), or 4 h 0.52 rad (30 degrees) head-up tilt (HUT). An important clinical observation was presyncopal symptoms in six of eight subjects following 4 h HDT, but in no subjects following 4 h HUT. Immediately prior to the OST, there were no differences in heart rate, stroke volume, cardiac output, mean arterial pressure and total peripheral resistance for HDT and HUT. However, stroke volume and cardiac output were greater for the control group. Mean arterial pressure for the control group was less than HDT but not HUT. Over the full 10-min period of OST, the mean arterial pressure was not different between groups. Heart rate increased to the same level for all three treatments. Stroke volume decreased across the full time period for control and HDT, but only at 3 and 9 min for HUT. There was a higher total peripheral resistance in the HDT group than control or HUT. The pre-ejection period to left ventricular ejection time ratio was less in HDT than for control or HUT groups. These data indicate a rapid adaptation of the cardiovascular system to 4 h HDT that appears to be inappropriate on reapplication of a head to foot gravity vector. We speculate that the cause of the impaired orthostatic tolerance is decreased tone in venous capacitance vessels so that venous return is inadequate.