Stress hypertension in monkeys

1. The influence of chronic forelimb immobilization enforcing movement in upright position on blood pressure was studied in monkeys. 2. In the course of 6 months all animals subjected to immobilization became hypertensive due to a parallel increase of systolic and diastolic pressure by about 30%. The hypertension was demonstrable both in awake and anaesthetized animals and persisted even after restitution of a normal movement regime. 3. In the chronic stage (after 15 months), the plasma renin concentration was decreased by 55%, indicating that the renin-angiotensin system activation does not participate in the maintenance of the hypertensive state. The plasma volume was diminished by 18%, while the interstitial fluid volume did not differ significantly from control values. 4. It is concluded that chronic forelimb immobilization in monkeys induces a low-renin hypertension, associated with changes in extracellular fluid compartments resembling the pattern found in the hypovolaemic type of essential hypertension.     

Influence of age on saline hypertension in subtotal nephrectomized rats

In uninephrectomised immature and adult male rats 34% renal tissue was removed from the remaining kidney and after 60-days exposure to saline treatment (0.17 mol/l NaCl solution as only drinking fluid) the mean arterial blood pressure, plasma urea concentration, plasma and extracellular fluid volumes were estimated. In comparison with water drinking uninephrectomised age-matched controls it has been found that: in both age groups, the loss of tissue from the remaining kidney was fully replaced by compensatory growth of the renal stump, plasma urea concentration remained unchanged in animals operated on when adult, but increased in animals operated on when immature, the interstitial fluid volume increased in both age groups--the plasma volume as well as blood pressure remained unchanged in animals treated when adult, but increased in animals treated when immature. It is concluded that under conditions of elevated salt intake the loss of renal mass in immature rats was compensated by growth of tissue with a lower excretory ability than in adult ones, this being responsible for the development of hypertension in the younger group.     

Body fluids and their distribution in experimental hypertension

The relation between blood pressure level and extracellular fluid volume and its distribution was studied in rats subjected to the following hypertensive stimuli--1K1C and 2K1C renal artery constriction, subtotal nephrectomy-salt and DOCA-salt. In all experimental groups the blood pressure increase was accompanied by increased extracellular fluid volume which was not always distributed proportionally between intravascular (PV) and interstitial (IFV) compartments. The blood pressure rise was further potentiated by plasma volume expansion so that the increased PV/IFV ratio was associated with a more pronounced hypertensive response (1K1C vs 2K1C, DOCA-salt vs subtotal nephrectomy-salt). However, adequate expansion of interstitial fluid is a necessary prerequisite for the hypertensive response. In DOCA-salt treated DI Brattleboro rats (lacking antidiuretic vasopressin action) plasma volume expansion per se was not accompanied by severe DOCA-salt hypertension. It is concluded that the expansion of both compartments of extracellular space, i.e. plasma volume and interstitial fluid volume, was necessary for a full development of severe hypertension. The expansion of only one of these compartments was accompanied by a mild blood pressure increase or blood pressure did not change significantly.     

The role of chloride in deoxycorticosterone hypertension: selective sodium loading by diet or drinking fluid

To evaluate the role of chloride in the pathogenesis of salt-dependent deoxycorticosterone (DOC) hypertension, we studied young Wistar rats chronically loaded with sodium bicarbonate (NaHCO(3)) or sodium chloride (NaCl) which were administered either in the diet or in the drinking fluid. Selective sodium loading (without chloride) increased blood pressure (BP) in DOC-treated animals only if NaHCO(3) was provided in the diet. In contrast, no significant blood pressure changes were induced by DOC treatment in rats drinking NaHCO(3) solution. Hypernatremia and high plasma osmolality occurred only in rats drinking NaCl or NaHCO(3) solutions. Compared to great volume expansion in NaCl-loaded DOC-treated rats, the degree of extracellular fluid volume expansion (namely of its interstitial fraction) was substantially lower in both NaHCO(3)-loaded groups in which significant hypokalemia was observed. NaHCO(3)-drinking rats without significant blood pressure response to DOC treatment represented the only experimental group in which blood volume was not expanded. In conclusion, our data confirm previous observations that NaHCO(3) loading is less potent in eliciting DOC hypertension than NaCl loading, but blood pressure rise in rats fed NaHCO(3) diet clearly demonstrated that selective sodium loading could potentiate the development of DOC hypertension if NaHCO(3) is offered within the appropriate dietary regimen. The reasons for the failure of NaHCO(3)-drinking rats to elevate blood pressure in response to chronic mineralocorticoid treatment are not obvious. However, the absence of a significant plasma volume expansion together with hypernatremia and increased plasma osmolality suggest a considerable degree of dehydration in these animals which fail to increase their fluid consumption compared to water drinking rats.     

Effects of pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) on the cardiovascular system in sheep.

The cardiovascular effects of PACAP and VIP were studied in intact conscious sheep; PACAP (0.008, 0.04, 0.2, and 1.0 nmol/min) and VIP (0.07, 0.2, 0.6, and 1.8 nmol/min) were infused in conscious sheep for periods of 10 min. For each peptide there was a dose-dependent increase in heart rate. At the highest doses tested, pulse pressure and mean arterial pressure tended to increase and decrease, respectively. However, only the decrease in mean arterial pressure following the highest dose of VIP reached significance. At the highest doses tested, heart rate increased nearly threefold during the infusion while mean arterial pressure declined by 18.5%. In individual animals the decrease in blood pressure and increase in heart rate occurred simultaneously, so that we were unable to conclude whether the increase in heart rate was due to a baroreceptor reflex.     

Adrenergic responses of the cardiovascular system of the eel, Anguilla australis, in vivo

Heart output, arterial pressures, and heart rate were measured directly in conscious unrestrained eels (Anguilla australis) and responses to intra-arterial injection of adrenaline monitored. Adrenaline increased systemic vascular resistance, heart output, and cardiac stroke volume in all animals. In some cases small transient decreases in stroke volume and hence heart output were seen at the peak of the pressor response: These probably reflect a passive decrease in systolic emptying due to increased afterload on the heart. In most cases, adrenaline produced tachycardia; but two animals showed consistent and profound reflex bradycardia, which was accompanied by a concomitant increase in stroke volume such that heart output was maintained or increased slightly. The interaction of changes in heart output and systemic vascular resistance produced complex and variable changes in arterial pressure. There was no consistent pattern of changes in branchial vascular resistance. Atropine treatment in vivo revealed vagal cardio-inhibitory tone in some animals and always blocked the reflex bradycardia seen during adrenaline induced hypertension. In some animals, adrenaline injection after atropine pretreatment led to the establishment of cyclic changes in arterial pressure with a period of about 1 min (Mayer waves).     

Abnormal regulation of the sympathoadrenal system in deoxycorticosterone acetate-salt hypertensive rats

With the use of circulating norepinephrine (NE) and epinephrine (E) levels, the sympathoadrenal activity as well as its local modulation by adrenoceptors were studied in normotensive (NT) and DOCA-salt hypertensive (HT) rats. In anesthetized hypertensive rats, plasma NE levels were higher, whereas in conscious animals both NE and E levels were found to be increased, suggesting an increased basal sympathoadrenal tone in these animals. The finding of a close correlation between blood pressure levels and NE levels suggests that the elevation of blood pressure may be linked to sympathetic system activity in this experimental model of hypertension. The reactivity of the sympathoadrenal system was also found to be increased in DOCA HT rats. Following a bilateral carotid occlusion of 1 min, which specifically activates the adrenal medulla, the elevation of E levels was found to be potentiated in intact or vagotomized HT rats. Moreover, in response to prolonged or acute hypotension in anesthetized and conscious animals, the elevation in plasma NE and E levels was found to be markedly potentiated in DOCA HT rats. The local modulating adrenoceptor-mediated mechanisms of the sympathoadrenal system appeared to be altered in this model of hypertension. Although it was possible to demonstrate that the E response to carotid occlusion can be greatly potentiated by administration of an alpha2-antagonist (yohimbine) and completely abolished by an alpha2-agonist (clonidine) in NT rats, the E response was found to be unaffected by the same treatments in HT rats, suggesting a reduced sensitivity in the alpha2-mediated inhibitory modulation of the adrenal medulla. Moreover, the acute treatment with a beta-blocker (sotalol) lowered circulating NE levels and blood pressure only in HT rats, suggesting the possibility of a more sensitive beta-receptor-mediated presynaptic facilitatory mechanism on sympathetic fibers of these animals. Finally, it was observed that the functional balance which exists between the activities of sympathetic fibers and the adrenal medulla in normotensive animals appears to be impaired in DOCA HT rats. In conclusion, the present studies suggest that the increased sympathoadrenal tone and reactivity may be due, in part, to a variety of dysfunctions in local adrenoceptor modulatory mechanisms of the sympathoadrenal system in DOCA hypertensive rats.     

Atrial natriuretic factor and body water distribution

In the rat, the effects of an atrial natriuretic factor (ANF) (Rat, 8-33 Peninsula Lab) on body water distribution have been evaluated. The ANF administration to nephrectomized animals produced a decrease in plasma volume and a slight increase in haematocrit and in plasma albumin concentration. No modifications were observed in total and intracellular water. The fluid efflux from the capillaries appeared to be located in the interstitial space. These results suggest that ANF could regulate plasma volume and systemic blood pressure, concurrently with its other known effects.     

Pharmacologic agents for the in vivo detection of vascular sodium transport defects in hypertension

Anatagonists to angiotensin, catecholamines, aldosterone, and vasopressin have long been used to help determine agonist roles in hypertension. We here call attention to a possible extension of this approach to detect, evaluate, and treat vascular sodium transport defects in hypertension. Two basic types of transport defects have been identified in the blood vessels of hypertensive animals, increased sodium permeability and decreased sodium pump activity. Intravenous injection of 6-iodo-amiloride, a sodium channel blocker and vasodilator, produces an immediate and sustained decrease in blood pressure in two genetic models of hypertension characterized by increased permeability of the vascular smooth muscle cell membrane to sodium (Okamoto spontaneously hypertensive rat, Dahl salt sensitive rat), whereas it produces only a transient fall in arterial pressure in two renal models of hypertension having normal sodium permeability in vascular smooth muscle cells (reduced renal mass-saline rat, one-kidney, one clip rat). Canrenone, a metabolic product of spironolactone which can compete with oubain for binding to Na+,K+-ATPase at the digitalis receptor site, decreases blood pressure in a low renin, volume expanded model of hypertension which has been shown to have depressed sodium pump activity in arteries and increased sodium pump inhibitor in plasma (reduced renal mass-saline rat) but has no effect on blood pressure in a genetic model of hypertension which has been shown to have increased sodium pump activity secondary to increased sodium permeability (spontaneously hypertensive rat). Thus, a sodium channel blocker and a competitor to ouabain binding can detect and determine the functional significance of sodium transport defects in the blood vessels of intact hypertensive animals. Studies in red and white blood cells suggest that similar defects may exist in the blood vessels of hypertensive humans. Thus, this approach, probing for vascular transport defects in the intact animal, may ultimately also be useful in the clinical setting.     

Effects of atrial natriuretic factor on blood pressure and the renin-angiotensin-aldosterone system

Atrial natriuretic factor (ANF) antagonizes vasoconstriction induced by numerous smooth muscle agonists and also lowers blood pressure in intact animals. ANF has particularly marked relaxant effects on angiotensin II-contracted vessels in vitro. Sensitivity to the blood pressure-lowering effect of ANF in vivo appears to be enhanced in renin-dependent models of renovascular hypertension compared with other experimental hypertensive models. The depressor action of low, possibly physiological doses of ANF in two-kidney, one-clip Goldblatt rats is due to a decrease in total peripheral resistance. On the other hand, high doses of ANF can lower cardiac output, particularly in volume-expanded models such as deoxycorticosterone-salt hypertension. ANF markedly inhibits renin secretion in intact animals, probably via increased glomerular filtration rate and load of sodium chloride to the macula densa. This effect is masked when renal perfusion is impaired (e.g., via unilateral renal artery constriction), in which case ANF may stimulate renin secretion slightly. ANF also reduces plasma aldosterone in vivo and inhibits basal and agonist-induced aldosterone release from isolated adrenal cortical cells. This effect appears to be especially marked for angiotensin-induced aldosterone production in vivo and in vitro. These findings indicate that ANF has potentially important interactions with the renin-angiotensin-aldosterone system and suggest a role for ANF in the homeostatic control of blood pressure as well as of extracellular fluid volume.     

Reversal of hemoglobin-induced vasoconstriction with sustained release of nitric oxide

Erythrocyte free hemoglobin (Hb) induces vasoconstriction due to nitric oxide (NO) scavenging, limiting the NO available for vascular smooth muscle. The central objective of this study was to restore NO bioavailability using long-lived circulating NO-releasing nanoparticles (NO-np) to reverse the vasoconstriction and hypertension induced by polymerized bovine Hb (PBH) NO scavenging. PBH (13 g/dl) was infused in a volume equal to 10% of the animal blood volume. Intravascular NO supplementation was provided with an infusion of NO-np (10 and 20 mg/kg body wt). This study was performed using the hamster window chamber model to concurrently access systemic and microvascular hemodynamics. Infusion of PBH increased blood pressure and induced vasoconstriction. Treatment with 10 and 20 mg/kg NO-np reduced the blood pressure and vasoconstriction induced by PBH. Moreover, the higher dose of NO-np decreased blood pressure and induced vasodilation compared with baseline, respectively. Treatment with NO-np to decrease PBH-induced vasoconstriction increased methemoglobin levels and plasma nitrite and nitrate. In conclusion, NO-np counteracted both systemic hypertension and decreased the vasoconstrictor effects of PBH infusion, improving systemic and microvascular function. Based on the observed physiological properties, NO-np has clear potential as a therapeutic agent to replenish NO in situations where NO production is impaired, insufficient, or consumed, thereby preventing vascular complications.     

VEGF-C attenuates renal damage in salt-sensitive hypertension

Salt-sensitive hypertension is a major risk factor for renal impairment leading to chronic kidney disease. High-salt diet leads to hypertonic skin interstitial volume retention enhancing the activation of the tonicity-responsive enhancer-binding protein (TonEBP) within macrophages leading to vascular endothelial growth factor C (VEGF-C) secretion and NOS3 modulation. This promotes skin lymphangiogenesis and blood pressure regulation. Whether VEGF-C administration enhances renal and skin lymphangiogenesis and attenuates renal damage in salt-sensitive hypertension remains to be elucidated. Hypertension was induced in BALB/c mice by a high-salt diet. VEGF-C was administered subcutaneously to high-salt-treated mice as well as control animals. Analyses of kidney injury, inflammation, fibrosis, and biochemical markers were performed in vivo. VEGF-C reduced plasma inflammatory markers in salt-treated mice. In addition, VEGF-C exhibited a renal anti-inflammatory effect with the induction of macrophage M2 phenotype, followed by reductions in interstitial fibrosis. Antioxidant enzymes within the kidney as well as urinary RNA/DNA damage markers were all revelatory of abolished oxidative stress under VEGF-C. Furthermore, VEGF-C decreased the urinary albumin/creatinine ratio and blood pressure as well as glomerular and tubular damages. These improvements were associated with enhanced TonEBP, NOS3, and lymphangiogenesis within the kidney and skin. Our data show that VEGF-C administration plays a major role in preserving renal histology and reducing blood pressure. VEGF-C might constitute an interesting potential therapeutic target for improving renal remodeling in salt-sensitive hypertension.     

The hemodynamic consequences of hemorrhage and hypernatremia in two amphibians

1. Graded hypovolemia was induced by hemorrhagic blood loss and graded hypernatremia by salt load in the toad, Bufo marinus, and the bullfrog, Rana catesbeiana. Maximal blood flow rates in the systemic arches and arterial and venous pressures were measured during activity after each stress. 2. Maximal blood flow rates in the B. marinus did not decline until blood loss exceeded 5% of initial body mass. In R. catesbeiana, losses of 2% initial body mass caused a decline (Fig. 1). 3. Maximal heart rates did not change with hemorrhage (Fig. 2). The decline in blood flow rates with hemorrhage was due to declining pulse volumes in both species (Fig. 3). 4. Arteriovenous pressure difference declined with hemorrhage in both species (Fig. 4). Peripheral resistance increased with hemorrhage in parallel with compromised blood flow rates (Fig. 5). 5. Plasma sodium concentration slightly increased with hemorrhage, while plasma protein concentration and hematocrit declined. Lymphatic compensation for hemorrhagic loss is indicated in both species (Fig. 6). 6. Induced hypernatremia compromised blood flow rates in both species at plasma sodium concentrations above 175 mM. The decline in flow rates was principally a result of a decrease in pulse volume, though maximal heart rates also declined (Figs. 2, 3, 7). 7. Induced hypernatremia had no effect on the arteriovenous pressure difference in B. marinus but caused it to decline in R. catesbeiana. Peripheral resistance increased in only B. marinus but not R. catesbeiana (Figs. 4, 5). Hematocrit did not change with salt load, indicative of a constant vascular volume.     

Acute volume expansion as a physiological stimulus for the release of atrial natriuretic peptides in the rat

The concentration of immunoreactive atrial natriuretic peptide(s) (ANP) was measured in normovolemic conscious rats and 15 min after 10% and 20% blood volume expansion. A 20% blood volume expansion caused a 2-fold increase in plasma ANP. While plasma ANP increased linearly, atrial levels of ANP remained unaltered. The increase in plasma ANP parallelled increases of central blood volume and central venous pressure. It is concluded that acute blood volume expansion is a major physiological stimulus for the release of atrial natriuretic peptides into the circulation.     

The cardiovascular paradox of pregnancy

Despite widespread accessibility to prenatal care, little is known on the mechanisms initiating early maternal adaptation to pregnancy. Moreover, preeclampsia and intrauterine growth retardation remain the most frequent and serious complications of pregnancy. Recent studies, both in humans and in laboratory animals, have shown that very early events in gestation may be important determinants for the continuation of healthy pregnancy. Certain of these early adaptations appear to be linked to the corpus luteum of pregnancy, as ovarian steroid hormones (especially progesterone) would set the basic hemodynamic conditions, more specifically, generalized vasodilation. This new hemodynamic setup initiates a vicious cycle in which the renin - angiotensin - aldosterone system is activated, together with the resetting of the control of antidiuretic hormone secretion relative to plasma osmolality. This leads to a gradual and substantial increase in plasma volume and a parallel increase in cardiac function (both heart rate and stroke volume) with the goal of maintaining blood pressure in the face of the generalised vasodilation. This includes the creation of a functional arterio-venous shunt represented by the utero-placental circulation. By the end of the first trimester, the decrease in peripheral vascular resistance is marked relative to the increase in cardiac output, resulting in a significant decrease in blood pressure that will be maintained until the third trimester. It is proposed that in preeclampsia, these very early events (vasodilation - increased plasma volume) fail to occur, resulting in an absence of the usual decrease in blood pressure, which is normally seen in the second trimester of pregnancy, and hypertension in the third trimester. Experimental animals, especially the rat, are suitable models to study this early maternal adaptation to pregnancy, since both endocrine and hemodynamic changes appear to be similar to humans.     

The distribution and metabolism of glycerol in the rabbit.

1. The effective volume of distribution of labelled glycerol was studied in conscious young adult rabbits provided with in-dwelling cannulae in the femoral blood vessels. This could be estimated after sampling arterial blood throughout an intravenous infusion of [2-3H]glycerol. The volume was calculated by using an algebraic method of graphical area analysis over 100 min of equilibration, and is symbolized 100V e or 100V e%. It occupied 34.1 +/- 2.2% (mean +/- S.E.M.; n = 13) of the body weight. The pool of endogenous glycerol occupying this space is distinguished in the present paper by calling it the transit pool, symbolized 100Me. 2. The median time of transit of glycerol through this pool was approx. 6 min in these conscious rabbits with normal (less than 0.2 mM) blood glycerol concentrations. 3. The metabolism of glycerol was also studied in rabbits while anaesthetized with urethane or while conscious. On average, half of the change in glycerol concentration that occurred on overnight starvation could be attributed to a decrease in clearance, whereas half was due to an increase in lipolysis. 4. The correlation between the reciprocal of glycerol concentration and clearance showed that in these animals about a quarter of the variation in concentration was due to an association with clearance. The remainder of the variation was attributed to variations in the rate of glycerol formation (lipolysis). 5. The regression of glycerol turnover rate on concentration implied that turnover was positive at zero glycerol concentration. This confirms previous findings from studies on other species. The explanation offered for this phenomenon is that the well-known physiological changes induced by feeding (decreased lipolysis, increased splanchnic blood flow) may independently decrease the glycerol concentration by both decreasing its release into the blood and simultaneously increasing its clearance.     

Blood pressure and hemodynamic responses after exercise in older hypertensives

Recently, systolic and diastolic blood pressure have been reported to be significantly lower for several hours after exercise than when measured at rest before exercise in individuals with essential hypertension. We sought to determine the hemodynamic mechanism underlying this reduction in blood pressure. Twenty-four men and women 60-69 yr of age with persistent essential hypertension completed one of the following protocols: exercise at 50% of maximum O2 consumption (VO2 max) followed by 1 h of recovery, exercise at 70% of VO2 max followed by 3 h of recovery, or a 4-h control study. Systolic pressure was significantly lower during recovery after both intensities of exercise, but diastolic pressure was unchanged. The lower blood pressure was primarily due to a reduction in cardiac output, since total peripheral resistance was increased throughout both recovery periods. Cardiac output was reduced in recovery because of a reduction in stroke volume. Heart rate was above, or no different from, that at rest before exercise. Changes in plasma volume could not entirely account for the reduction in stroke volume. Therefore, other mechanisms altering venous return and/or myocardial contractility appear to be responsible for the reduction in systolic blood pressure evident after a single bout of submaximal exercise in individuals with essential hypertension.     

Effect of alveolar liquid on distribution of blood flow in dog lungs.

Previous studies have shown that a shift in blood flow away from edematous regions does not occur until the alveoli contain liquid. The present experiments were designed to examine the separate effect of air space liquid, air space plus interstitial liquid, and reduced lung volume on blood flow. We found that reduced lung volume was not associated with significant changes in blood flow and that no systematic change in blood flow occurred when alveoli were filled with isosmotic liquid (autologous plasma). However, when hyposmotic liquid (dilute plasma) was instilled so that both the air space and the alveolar wall interstitial space were filled, blood flow was systematically reduced. This suggested that interstitial liquid was responsible raising vascular resistance in these experiments and that it might also be important in raising local vascular resistance in pulmonary edema. This latter hypothesis was tested in isolated perfused lobes where rapid freezing and quantitative histology showed that the number of open capillaries was significantly reduced in the liquid-filled alveoli (P less than 0.001). These observations suggest that interstitial pressure rises in pulmonary edema with the result that the transmural pressure of the alveolar vessels falls and vascular resistance is increased.     

Systemic and renal hemodynamic responses to vascular blockade of vasopressin in conscious dogs with ascites

A role for arginine vasopressin has been implicated in the compensatory control of arterial blood pressure in several animal models with reported increases in plasma levels of arginine vasopressin. A threefold elevation in plasma vasopressin has been reported in conscious dogs following constriction of the inferior vena cava. In the present study, infusion of the arginine vasopressin antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-O-methyltyrosine] Arg8-vasopressin into conscious dogs with chronic caval constriction did not decrease mean arterial blood pressure. However, the dose of infused antagonist completely blocked the pressor response to 2 micrograms of exogenous vasopressin. Also the antagonist produced no effect on heart rate, plasma renin activity, or urinary volume and electrolyte excretions. A slight, transient increase (P less than or equal to 0.05) was observed in creatinine clearance and in PAH clearance following antagonist infusion, suggesting a possible decrease in renal vascular resistance. These data suggest that the direct vasoconstrictor actions of vasopressin contribute minimally, if at all, to blood pressure maintenance following chronic caval constriction. Alternatively, blockade of endogenous vasopressin receptors at the level of peripheral arterioles may have resulted in no depressor response due to a masking of this response by other compensatory hormonal and neural pressor systems.     

Pregnancy alters hemodynamic responses to hemorrhage in conscious rabbits

Pregnant animals are less able to maintain mean arterial pressure (MAP) during hemorrhage compared with nonpregnant animals, but the hemodynamic basis of this difference is unknown. The hypothesis that pregnancy attenuates responses of cardiac output, as well as total peripheral resistance (TPR) and femoral conductance, to hemorrhage was tested in conscious rabbits in both the pregnant and nonpregnant state (n = 10). During continuous slow blood loss (2% of the initial blood volume per minute), MAP was maintained initially in both groups. However, MAP then abruptly decreased to <45 mmHg in all animals after a smaller percentage of the initial blood volume was removed in pregnant compared with nonpregnant rabbits (43.6 +/- 1.7%, nonpregnant; 29.6 +/- 2.2%, pregnant; P < 0.005). The more rapid transition to hypotension exhibited by pregnant rabbits was associated with greater initial falls in cardiac output (-56 +/- 10 ml/min, nonpregnant; -216 +/- 33 ml/min, pregnant; P < 0.005) and stroke volume (0.8 +/- 0.1 ml/beat, nonpregnant; -1.3 +/- 0.1 ml/beat, pregnant; P < 0.05). In addition, the increase in TPR as a function of the decrease in cardiac output was markedly attenuated (P < 0.0001) during pregnancy. Whereas femoral conductance decreased in nonpregnant rabbits, it did not change significantly in pregnant animals. In conclusion, the lesser ability of conscious pregnant rabbits to maintain MAP during hemorrhage is due largely to a greater decrease in cardiac output but also to inadequate reflex increases in TPR, possibly in part in the femoral vascular bed.