Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion.

Atrial natriuretic peptide (ANP) may activate multiple mechanisms that protect against circulatory volume overload. We hypothesized that a temporal relationship exists between increases in cardiac filling pressure and plasma ANP concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). We infused 30 ml/kg isotonic saline at 100 ml/min in seven supine male subjects and monitored responses for 3 h postinfusion. Right atrial pressure (RAP) was measured via a central catheter. ANP (pmol/l) was measured by radioimmunoassay. Transcapillary fluid transport (TFT) equaled infused volume minus UV, insensible fluid loss, and change in plasma volume (PV, measured with Evan's blue). Systemic vascular resistance (SVR) was calculated as (mean arterial pressure-RAP)/cardiac output (determined by acetylene rebreathing). Plasma oncotic pressure (OP) was measured directly. During infusion, mean TFT (+/- SE) increased from net reabsorption during control of 111 +/- 27 ml/h to net filtration of 1,219 +/- 143 ml/h (P < 0.01). At end infusion, mean RAP, heart rate, and PV exhibited peak increases of 146, 23, and 27%, respectively. Concurrently, SVR and OP achieved nadirs 29 and 31% below control, respectively. Mean plasma ANP and UV peaked (45 and 390%, respectively) at 30 min postinfusion. Systemic vasodilation and capillary filtration resulted from and compensated for infusion-induced circulatory pressure increases and hemodilution. By 1 h postinfusion, most cardiovascular variables had returned toward control levels, and net reabsorption of extravascular fluid ensued.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma volume expansion in humans after a single intense exercise protocol.

We used intense intermittent exercise to produce a 10% expansion of plasma volume (PV) within 24 h and tested the hypothesis that PV expansion is associated with an increase in plasma albumin content. The protocol consisted of eight 4-min bouts of exercise at 85% maximal O2 uptake with 5-min recovery periods between bouts. PV, plasma concentrations of albumin and total protein (TP), and plasma osmolality were measured before and during exercise and at 1, 2, and 24 h of recovery from exercise. During exercise, PV decreased by 15%, while plasma TP and albumin content remained at control levels. At 1 h of recovery, plasma albumin content was elevated by 0.17 +/- 0.04 g/kg body wt, accounting for the entire increase in plasma TP content. PV returned to control level at 1 h of recovery without fluid intake by the subjects, despite a 820 +/- 120-g reduction in body weight. At 2 h of recovery, plasma TP content remained significantly elevated, and plasma TP and albumin concentration were significantly elevated. At 24 h of recovery, PV was expanded by 4.5 +/- 0.7 ml/kg body wt (10 +/- 1%), estimated from hematocrit and hemoglobin changes, and by 3.8 +/- 1.3 ml/kg body wt (8 +/- 3%), measured by Evans blue dye dilution. Plasma albumin content was increased by 0.19 +/- 0.05 g/kg body wt at 24 h of recovery. If 1 g of albumin holds 18 ml of water, this increase in plasma albumin content can account for a 3.4-ml/kg body wt expansion of the PV. No significant changes in plasma osmolality occurred during recovery, but total plasma osmotic content increased in proportion to PV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of polycythemia on blood volume and thermoregulation during exercise-heat stress

We studied the effects of autologous erythrocyte infusion on blood volume and thermoregulation during exercise in the heat. By use of a double-blind design, nine unacclimated male subjects were infused with either 600 ml of a NaCl-glucose-phosphate solution containing a approximately 50% hematocrit (n = 6, reinfusion) or 600 ml of this solution only (n = 3, saline). A heat stress test (HST) was attempted approximately 2-wk pre- and 48-h postinfusion during the late spring months. After 30 min of rest in a 20 degrees C antechamber, the HST consisted of a 120-min exposure (2 repeats of 15 min rest and 45 min treadmill walking) in a hot (35 degrees C, 45% rh) environment while euhydrated. Erythrocyte volume (RCV, 51Cr) and plasma volume (PV, 125I) were measured 24 h before each HST, and maximal O2 uptake (VO2max) was measured 24 h after each HST. Generally, no significant effects were found for the saline group. For the reinfusion group, RCV (11%, P less than 0.01) and VO2max (11%, P less than 0.05) increased after infusion, and the following observations were made: 1) the increased RCV was associated with a reduction in PV to maintain the same blood volume as during the preinfusion measurements; 2) polycythemia reduced total circulating protein but did not alter F-cell ratio, plasma osmolality, plasma protein content, or plasma lactate at rest or during exercise-heat stress; 3) polycythemia did not change the volume of fluid entering the intravascular space from rest to exercise-heat stress; and 4) polycythemia tended to reduce the rate of heat storage during exercise-heat stress.     

Heat acclimation improves regulation of plasma volume and plasma Na(+) content during exercise in horses.

This study determined the plasma volume (PV) and ion responses to heat acclimation and exercise in six trained Thoroughbred horses during 21 days of exposure to heat and humidity (33 degrees C, 83% relative humidity) for 4 h/day. During the 2nd h on days 0, 3, 7, 14, and 21, horses performed a standardized treadmill test, running at 50% of peak O(2) uptake until pulmonary artery temperature reached 41.5 degrees C. Heat acclimation resulted in an increase in PV from 21.3 +/- 1.1 liters on day 0 to 24.3 +/- 1.0 liters on day 14, returning to 22.6 +/- 0.9 liters on day 21. The corresponding total plasma protein contents were 1,273 +/- 53, 1,455 +/- 81, and 1,377 +/- 57 g, respectively, and increases in total plasma Na(+) plus Cl(-) content were 5,145 +/- 126, 5,749 +/- 146, and 5,394 +/- 114 mmol, respectively. Thus changes in PV were accompanied by direct changes in plasma protein and osmolyte contents. With exercise on day 0, PV decreased by 7.1 +/- 0.7% at 5 min of exercise and remained decreased (-6.7 +/- 1.3%) at 5 min of recovery. By day 21, PV decreased significantly less than on day 0 (by 5.2 +/- 0.9% at 5 min of exercise), was decreased by only 2.0 +/- 1.6% at 5 min of recovery, and was fully restored at 15 min of recovery. Plasma Na(+) concentration increased 3 meq/l during the first 5 min of exercise and was normalized by 5 min of recovery on day 0 and by end exercise on day 21. It is concluded that improved ability to regulate PV during exercise in response to heat acclimatization is associated with an increased PV and an improved conservation of Na(+).     

Angiotensin acts at the subfornical organ to increase plasma oxytocin concentrations in the rat

We have examined the effects of systemic angiotensin II (AII) on plasma oxytocin (OXY) concentrations in freely moving male Sprague-Dawley rats. We have also examined the role of the subfornical organ (SFO) as a CNS site at which circulating AII acts to influence secretion of this neurohypophysial peptide. OXY concentrations were measured by radioimmunoassay in plasma samples obtained by drawing blood samples through indwelling atrial catheters. In SFO intact animals (n = 8) AII infusion (1.0 microgram/kg/min) resulted in increases in plasma OXY concentrations from baseline values of 6.8 +/- 2.5 pg/ml to postinfusion concentrations of 44.9 +/- 11.9 pg/ml. In a second series of experiments electrolytic lesions were placed in the region of the SFO prior to testing the effects of AII infusion on OXY concentrations. Two further experimental groups were thus established according to the histologically verified location of lesions in either the rostral or caudal SFO. In the caudal SFO lesioned group AII infusion resulted in increases in plasma OXY concentrations from control values of 6.9 +/- 1.4 pg/ml to postinfusion levels of 45.1 +/- 9.8 pg/ml. These changes were not significantly different from the SFO intact group. In contrast rostral SFO lesions resulted in significantly elevated basal concentrations of OXY (17.4 +/- 3.4 pg/ml, n = 6) while postinfusion concentrations were found to be 22.8 +/- 4.9 pg/ml indicating that AII infusion was without effect following such lesions. These data are in accordance with the hypothesis that circulating AII acts at the SFO to influence SFO efferents which in turn activate OXY secreting neurons in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei. These neuroendocrine cells then release this peptide into the systemic circulation from the posterior pituitary.     

Progesterone increases plasma volume independent of estradiol.

Adequate plasma volume (PV) and extracellular fluid (ECF) volume are essential for blood pressure and fluid regulation. We tested the hypotheses that combined progesterone (P(4))-estrogen (E(2)) administration would increase ECF volume with proportional increases in PV, but that P(4) would have little independent effect on either PV or ECF volume. We further hypothesized that this P(4)-E(2)-induced fluid expansion would be a function of renin-angiotensin-aldosterone system stimulation. We suppressed P(4) and E(2) with a gonadotropin-releasing hormone (GnRH) antagonist in eight women (25 +/- 2 yr) for 16 days; P(4) (200 mg/day) was added for days 5-16 (P(4)) and 17beta-estradiol (2 x 0.1 mg/day patches) for days 13-16 (P(4)-E(2)). On days 2 (GnRH antagonist), 9 (P(4)), and 16 (P(4)-E(2)), we estimated ECF and PV. To determine the rate of protein and thus water movement across the ECF, we also measured transcapillary escape rate of albumin. In P(4), P([P(4)]) increased from 2.5 +/- 1.3 to 12.0 +/- 2.8 ng/ml (P < 0.05) with no change in P([E(2)]) (21.5 +/- 9.4 to 8.6 +/- 2.0 pg/ml). In P(4)-E(2), plasma concentration of P(4) remained elevated (11.3 +/- 2.7 ng/ml) and plasma concentration of E(2) increased to 254.1 +/- 52.7 pg/ml (P < 0.05). PV increased during P(4) (46.6 +/- 2.5 ml/kg) and P(4)-E(2) (48.4 +/- 3.9 ml/kg) compared with GnRH antagonist (43.3 +/- 3.2 ml/kg; P < 0.05), as did ECF (206 +/- 19, 244 +/- 25, and 239 +/- 27 ml/kg for GnRH antagonist, P(4), and P(4)-E(2), respectively; P < 0.05). Transcapillary escape rate of albumin was lowest during P(4)-E(2) (5.8 +/- 1.3, 3.5 +/- 1.7, and 2.2 +/- 0.4%/h for GnRH antagonist, P(4), and P(4)-E(2), respectively; P < 0.05). Serum aldosterone increased during P(4) and P(4)-E(2) compared with GnRH antagonist (79 +/- 17, 127 +/- 13, and 171 +/- 25 pg/ml for GnRH antagonist, P(4), and P(4)-E(2), respectively; P < 0.05), but plasma renin activity and plasma concentration of ANG II were only increased by P(4)-E(2). This study is the first to isolate P(4) effects on ECF; however, the mechanisms for the ECF and PV expansion have not been clearly defined.     

Effect of exercise hemoconcentration and hyperosmolality on exercise responses

We investigated the effects of a decrease in plasma volume (PV) and an increase in plasma osmolality during exercise on circulatory and thermoregulatory responses. Six subjects cycled at approximately 65% of their maximum O2 uptake in a warm environment (30 degrees C, 40% relative humidity). After 30 min of control (C) exercise (no infusion), PV decreased 13.0%, or 419 +/- 106 (SD) ml, heart rate (HR) increased to 167 +/- 3 beats/min, and esophageal temperature (Tes) rose to 38.19 +/- 0.09 degrees C (SE). During infusion studies (INF), infusates were started after 10 min of exercise. The infusates contained 5% albumin suspended in 0.45, 0.9, or 3.0% saline. The volume of each infusate was adjusted so that during the last 10 min of exercise PV was maintained at the preexercise level and osmolality was allowed to differ. HR was significantly lower (10-16 beats/min) during INF than during C. Tes was reduced significantly during INF, with trends for increased skin blood flow and decreased sweating rates. No significant differences in HR, Tes, or sweating rate occurred between the three infusion conditions. We conclude that the decrease in PV, which normally accompanies moderate cycle exercise, compromises circulatory and thermal regulations. Increases in osmolality appear to have small if any effects during such short-term exercise.     

Exercise stroke volume relative to plasma-volume expansion

The effects of plasma-volume (PV) expansion on stroke volume (SV) (CO2 rebreathing) during submaximal exercise were determined. Intravenous infusion of 403 +/- 21 ml of a 6% dextran solution before exercise in the upright position increased SV 11% (i.e., 130 +/- 6 to 144 +/- 5 ml; P less than 0.05) in untrained males (n = 7). Further PV expansion (i.e., 706 +/- 43 ml) did not result in a further increase in SV (i.e., 145 +/- 4 ml). SV was somewhat higher during supine compared with upright exercise when blood volume (BV) was normal (i.e., 138 +/- 8 vs. 130 +/- 6 ml; P = 0.08). PV expansion also increased SV during exercise in the supine position (i.e., 138 +/- 8 to 150 +/- 8 ml; P less than 0.05). In contrast to these observations in untrained men, PV expansion of endurance-trained men (n = 10), who were naturally PV expanded, did not increase SV during exercise in the upright or supine positions. When BV in the untrained men was increased to match that of the endurance-trained subjects, SV was observed to be 15% higher (165 +/- 7 vs. 144 +/- 5 ml; P less than 0.05), whereas mean blood pressure and total peripheral resistance were significantly lower (P less than 0.05) in the trained compared with untrained subjects during upright exercise at a similar heart rate. The present findings indicate that exercise SV in untrained men is preload dependent and that increases in exercise SV occur in response to the first 400 ml of PV expansion. It appears that approximately one-half of the difference in SV normally observed between untrained and highly endurance-trained men during upright exercise is due to a suboptimal BV in the untrained men.     

Effect of rehydration on atrial natriuretic peptide release during exercise in the heat

In an attempt to investigate their relationships with plasma volume (PV), heart rate (HR), and other hormonal systems, plasma atrial natriuretic peptide (ANP) levels were determined in response to exercise in the heat, associated with dehydration and rehydration with various fluids. Five normal subjects underwent four 3-h experiments, in a 36 degree C environment, in which 25-min exercise periods on a cycle ergometer at 90 W alternate with 5-min rest periods. Blood samples were collected hourly and ANP, arginine vasopressin (AVP), adrenocorticotropin (ACTH), and cortisol were analyzed in four experimental sessions: without fluid supplement (DH) and with progressive rehydration either with water (W), acid isotonic solution (AISO), or neutral isotonic solution (NISO). Exercise in the heat, accompanied by a decrease in PV and an increase in osmolality, elicited an increase of 28 +/- 1.6 pg/ml in plasma ANP, with concomitant increases in AVP (5.1 +/- 1.4 pg/ml), ACTH (49.6 +/- 12.3 pg/ml), and cortisol (8.4 +/- 2.0 micrograms/100 ml). Progressive rehydration maintained PV and blunted ANP, AVP, ACTH, and cortisol responses. These results demonstrate the importance of rehydration, during exercise in a warm environment, in preventing hormonal increases. They suggest that under our conditions, the PV changes and the inferred atrial pressure changes may not be the primary factors controlling ANP release, as under other physiological conditions. The exercise-related activation of pituitary and adrenals and the stimulation of HR counteract the influence of PV changes due to vascular fluid shifts.     

Estrogen and progesterone effects on transcapillary fluid dynamics

The purpose of this study was to determine estrogen (E(2)) and progesterone (P(4)) effects on atrial natriuretic peptide (ANP) control of plasma volume (PV) and transcapillary fluid dynamics. To this end, we suppressed reproductive function in 12 women (age 21-35 yr) using a gonadotropin releasing-hormone (GnRH) analog (leuprolide acetate) for 5 wk. During the 5th week, the women either received 4 days of E(2) administration (17beta-estradiol, transdermal patch, 0.1 mg/day) or 4 days of E(2) with P(4) administration (vaginal gel, 90 mg P(4) twice per day). At the end of the 4th and 5th week of GnRH analog and hormone administration, we determined PV (Evans blue dye) and changes in PV and forearm capillary filtration coefficient (CFC) during a 120-min infusion of ANP (5 ng x kg body wt(-1) x min(-1)). Preinfusion PV was estimated from Evans blue dye measurement taken over the last 30 min of infusion based on changes in hematocrit. E(2) treatment did not affect preinfusion PV relative to GnRH analog alone (45.3 +/- 3.1 vs. 45.4 +/- 3.1 ml/kg). During ANP infusion CFC was greater during E(2) treatment compared with GnRH analog alone (6.5 +/- 1.4 vs. 4.9 +/- 1.4 microl. 100 g(-1) x min(-1) mmHg(-1), P < 0.05). The %PV loss during ANP infusion was similar for E(2) and GnRH analog-alone treatments (-0.8 +/- 0.2 and -1.0 +/- 0.2 ml/kg, respectively), indicating the change in CFC had little systemic effect on ANP-related changes in PV. Estimated baseline PV was reduced by E(2)-P(4) treatment. During ANP infusion CFC was approximately 30% lower during E(2)-P(4) (6.0 +/- 0.5 vs. 4.3 +/- 4.3 microl. 100 g(-1) x min(-1) mm Hg(-1), P < 0.05), and the PV loss during ANP infusion was attenuated (-0.9 +/- 0.2 and -0.2 +/- 0.2 ml/kg for GnRH analog-alone and E(2)-P(4) treatments, respectively). Thus the E(2)-P(4) treatment lowered CFC and reduced PV loss during ANP infusion.     

Volume expansion during NOS substrate donation with L-arginine: regulatory offsetting of renal response?

The responses to infusion of nitric oxide synthase substrate (L-arginine 3 mg.kg(-1).min(-1)) and to slow volume expansion (saline 35 ml/kg for 90 min) alone and in combination were investigated in separate experiments. L-Arginine left blood pressure and plasma ANG II unaffected but decreased heart rate (6 +/- 2 beats/min) and urine osmolality, increased glomerular filtration rate (GFR) transiently, and caused sustained increases in sodium excretion (fourfold) and urine flow (0.2 +/- 0.0 to 0.7 +/- 0.1 ml/min). Volume expansion increased arterial blood pressure (102 +/- 3 to 114 +/- 3 mmHg), elevated GFR persistently by 24%, and enhanced sodium excretion to a peak of 251 +/- 31 micromol/min, together with marked increases in urine flow, osmolar and free water clearances, whereas plasma ANG II decreased (8.1 +/- 1.7 to 1.6 +/- 0.3 pg/ml). Combined volume expansion and L-arginine infusion tended to increase arterial blood pressure and increased GFR by 31%, whereas peak sodium excretion was enhanced to 335 +/- 23 micromol/min at plasma ANG II levels of 3.0 +/- 1.1 pg/ml; urine flow and osmolar clearance were increased at constant free water clearance. In conclusion, L-arginine 1) increases sodium excretion, 2) decreases basal urine osmolality, 3) exaggerates the natriuretic response to volume expansion by an average of 50% without persistent changes in GFR, and 4) abolishes the increase in free water clearance normally occurring during volume expansion. Thus L-arginine is a natriuretic substance compatible with a role of nitric oxide in sodium homeostasis, possibly by offsetting/shifting the renal response to sodium excess.     

Influence of acute plasma volume expansion on VO2 kinetics, VO2 peak, and performance during high-intensity cycle exercise.

The purpose of this study was to examine the influence of acute plasma volume expansion (APVE) on oxygen uptake (V(O2)) kinetics, V(O2peak), and time to exhaustion during severe-intensity exercise. Eight recreationally active men performed "step" cycle ergometer exercise tests at a work rate requiring 70% of the difference between the gas-exchange threshold and V(O2max) on three occasions: twice as a "control" (Con) and once after intravenous infusion of a plasma volume expander (Gelofusine; 7 ml/kg body mass). Pulmonary gas exchange was measured breath by breath. APVE resulted in a significant reduction in hemoglobin concentration (preinfusion: 16.0 +/- 1.0 vs. postinfusion: 14.7 +/- 0.8 g/dl; P < 0.001) and hematocrit (preinfusion: 44 +/- 2 vs. postinfusion: 41 +/- 3%; P < 0.01). Despite this reduction in arterial O(2) content, APVE had no effect on V(O2) kinetics (phase II time constant, Con: 33 +/- 15 vs. APVE: 34 +/- 12 s; P = 0.74), and actually resulted in an increased V(O2peak) (Con: 3.90 +/- 0.56 vs. APVE: 4.12 +/- 0.55 l/min; P = 0.006) and time to exhaustion (Con: 365 +/- 58 vs. APVE: 424 +/- 64 s; P = 0.04). The maximum O(2) pulse was also enhanced by the treatment (Con: 21.3 +/- 3.4 vs. APVE: 22.7 +/- 3.4 ml/beat; P = 0.04). In conclusion, APVE does not alter V(O2) kinetics but enhances V(O2peak) and exercise tolerance during high-intensity cycle exercise in young recreationally active subjects.     

Increased renal tubular sodium reabsorption during exercise-induced hypervolemia in humans.

We tested the hypothesis that renal tubular Na(+) reabsorption increased during the first 24 h of exercise-induced plasma volume expansion. Renal function was assessed 1 day after no-exercise control (C) or intermittent cycle ergometer exercise (Ex, 85% of peak O(2) uptake) for 2 h before and 3 h after saline loading (12.5 ml/kg over 30 min) in seven subjects. Ex reduced renal blood flow (p-aminohippurate clearance) compared with C (0.83 +/- 0.12 vs. 1.49 +/- 0.24 l/min, P < 0.05) but did not influence glomerular filtration rates (97 +/- 10 ml/min, inulin clearance). Fractional tubular reabsorption of Na(+) in the proximal tubules was higher in Ex than in C (P < 0.05). Saline loading decreased fractional tubular reabsorption of Na(+) from 99.1 +/- 0.1 to 98.7 +/- 0.1% (P < 0.05) in C but not in Ex (99.3 +/- 0.1 to 99.4 +/- 0.1%). Saline loading reduced plasma renin activity and plasma arginine vasopressin levels in C and Ex, although the magnitude of decrease was greater in C (P < 0.05). These results indicate that, during the acute phase of exercise-induced plasma volume expansion, increased tubular Na(+) reabsorption is directed primarily to the proximal tubules and is associated with a decrease in renal blood flow. In addition, saline infusion caused a smaller reduction in fluid-regulating hormones in Ex. The attenuated volume-regulatory response acts to preserve distal tubular Na(+) reabsorption during saline infusion 24 h after exercise.     

Effect of saline infusion during exercise on thermal and circulatory regulations

To quantify the effect of an acute increase in plasma volume (PV) on forearm blood flow (FBF), heart rate (HR), and esophageal temperature (Tes) during exercise, we studied six male volunteers who exercised on a cycle ergometer at 60% of maximal aerobic power for 50 min in a warm [(W), 30 degrees C, less than 30% relative humidity (rh)] or cool environment [(C), 22 degrees C, less than 30% rh] with isotonic saline infusion [Inf(+)] or without infusion [Inf(-)]. The infusion was performed at a constant rate of 0.29 ml.kg body wt-1.min-1 for 20-50 min of exercise to mimic fluid intake during exercise. PV decreased by approximately 5 ml/kg body wt within the first 10 min of exercise in all protocols. Therefore, PV in Inf(-) was maintained at the same reduced level by 50 min of exercise in both ambient temperatures, whereas PV in Inf(+) increased toward the preexercise level and recovered approximately 4.5 ml/kg body wt by 50 min in both temperatures. The restoration of PV during exercise suppressed the HR increase by 6 beats/min at 50 min of exercise in W; however, infusion had no effect on HR in C. In W, FBF in Inf(+) continued to increase linearly as Tes rose to 38.1 degrees C by the end of exercise, whereas FBF in Inf(-) plateaued when Tes reached approximately 37.7 degrees C. The infusion in C had only a minor effect on FBF.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of ACTH1-24 or cortisol on pulmonary maturation in the adrenalectomized ovine fetus

Pulmonary maturation in 8 ovine fetuses bilaterally adrenalectomized at 98-101 days and infused at term with either ACTH1-24 or cortisol was compared with that in 4 untreated sham-operated controls. Four of the adrenalectomized fetuses were infused intravascularly with ACTH1-24 5 micrograms/h for 84 h before delivery and the other four were infused with cortisol 1 mg/h for 72 h. The high plasma concentrations of immunoreactive ACTH in the adrenalectomized fetuses (2762 +/- 1339 ng/l, mean +/- SD) were not significantly elevated by infusion of ACTH1-24 but were markedly depressed by infusion of cortisol. Distensibility (V40) of the lungs was less than that of controls in both the ACTH1-24-infused and cortisol-infused fetuses (1.86 +/- 0.31 ml/g vs 0.62 +/- 0.13 ml/g and 1.27 +/- 0.34 ml/g respectively) but it was significantly greater in the cortisol-infused fetuses compared to those infused with ACTH1-24. The volume of air retained at 5 cm H2O pressure (V5) during deflation was markedly reduced in adrenalectomized fetuses (controls 1.14 +/- 0.52 ml/g vs 0.25 +/- 0.25 ml/g and 0.12 +/- 0.6 ml/g). The wet weight of the lungs and the concentrations of saturated phosphatylcholine in lung tissue and lavage fluid were lower in the adrenalectomized fetuses than in controls but the differences were not significant. It is concluded that infusion of ACTH1-24 at term in adrenalectomized fetuses is probably without effect whereas cortisol enhances distensibility.     

Plasma volume expansion does not increase maximal cardiac output or VO2 max in lowlanders acclimatized to altitude

With altitude acclimatization, blood hemoglobin concentration increases while plasma volume (PV) and maximal cardiac output (Qmax) decrease. This investigation aimed to determine whether reduction of Qmax at altitude is due to low circulating blood volume (BV). Eight Danish lowlanders (3 females, 5 males: age 24.0 +/- 0.6 yr; mean +/- SE) performed submaximal and maximal exercise on a cycle ergometer after 9 wk at 5,260 m altitude (Mt. Chacaltaya, Bolivia). This was done first with BV resulting from acclimatization (BV = 5.40 +/- 0.39 liters) and again 2-4 days later, 1 h after PV expansion with 1 liter of 6% dextran 70 (BV = 6.32 +/- 0.34 liters). PV expansion had no effect on Qmax, maximal O2 consumption (VO2), and exercise capacity. Despite maximal systemic O2 transport being reduced 19% due to hemodilution after PV expansion, whole body VO2 was maintained by greater systemic O2 extraction (P < 0.05). Leg blood flow was elevated (P < 0.05) in hypervolemic conditions, which compensated for hemodilution resulting in similar leg O2 delivery and leg VO2 during exercise regardless of PV. Pulmonary ventilation, gas exchange, and acid-base balance were essentially unaffected by PV expansion. Sea level Qmax and exercise capacity were restored with hyperoxia at altitude independently of BV. Low BV is not a primary cause for reduction of Qmax at altitude when acclimatized. Furthermore, hemodilution caused by PV expansion at altitude is compensated for by increased systemic O2 extraction with similar peak muscular O2 delivery, such that maximal exercise capacity is unaffected.     

Role of volume and prostaglandin synthesis in the suppression of renin by saline in the rat

To evaluate the contribution of plasma volume expansion per se on acute inhibition of renin release by sodium chloride infusion, renin responses to comparable plasma volume expansion with intravenous infusions of sodium chloride, sodium bicarbonate, or albumin were studied in separate groups of sodium chloride-depleted rats. In addition, urinary prostaglandin E2 (PGE2) excretion rate was compared in the saline- and sodium bicarbonate-infused animals to evaluate the relationship between acute changes in renin release and intrarenal PGE2 synthesis. All three groups were plasma volume-expanded by approximately 55%. Plasma renin activity (PRA) decreased in response to saline (12.3 +/- 1.0 to 6.7 +/- 0.7 ng AI/ml/hr; P less than 0.01) whereas PRA did not change with sodium bicarbonate (11.3 +/- 1.4 to 10.2 +/- 1.5) or albumin (9.9 +/- 0.7 to 8.2 +/- 1.0). The rate of PGE2 excretion was not changed by either saline (72.2 +/- 13.1 to 72.3 +/- 18.7 pg/min) or sodium bicarbonate infusion (70.7 +/- 8.8 to 64.9 +/- 7.0). These results support the hypothesis that acute suppression of PRA by infusion of saline is not dependent upon volume expansion per se. In confirmation of earlier observations, inhibition of renin release by sodium chloride was related to chloride. Finally, the results suggest that the renal tubular mechanism for inhibition of renin release by sodium chloride is not related to overall changes in renal PGE2 synthesis in the rat.     

Methods for assessing hepatic distending pressure and changes in hepatic capacitance in pigs

The equilibrium pressure obtained during simultaneous occlusion of hepatic vascular inflow and outflow was taken as the reference estimate of hepatic vascular distending pressure (P(hd)). P(hd) at baseline was 1.1 +/- 0.2 (mean +/- SE) mmHg higher than hepatic vein pressure (P(hv)) and 0.7 +/- 0.3 mmHg lower than portal vein pressure (P(pv)). Norepinephrine (NE) infusion increased P(hd) by 1. 5 +/- 0.5 mmHg and P(pv) by 3.7 +/- 0.6 mmHg but did not significantly increase P(hv). Hepatic lobar vein pressure (P(hlv)) measured by a micromanometer tipped 2-Fr catheter closely resembled P(hd) both at baseline and during NE-infusion. Dynamic pressure-volume (PV) curves were constructed from continuous measurements of P(hv) and hepatic blood volume increases (estimated by sonomicrometry) during brief occlusions of hepatic vascular outflow and compared with static PV curves constructed from P(hd) determinations at five different hepatic volumes. Estimates of hepatic vascular compliance and changes in unstressed blood volume from the two methods were in close agreement with hepatic compliance averaging 32 +/- 2 ml. mmHg(-1). kg liver(-1). NE infusion reduced unstressed blood volume by 110 +/- 38 ml/kg liver but did not alter compliance. In conclusion, P(hlv) reflects hepatic distending pressure, and the construction of dynamic PV curves is a fast and valid method for assessing hepatic compliance and changes in unstressed blood volume.     

Effects of estrogen and progesterone administration on extracellular fluid.

To determine the effect of estrogen and progesterone on plasma volume (PV) and extracellular fluid volume (ECFV), we suppressed endogenous estrogen and progesterone by using the gonadotropin-releasing hormone (GnRH) antagonist ganirelix acetate in seven healthy women (22 +/- 1 yr). Subjects were administered GnRH antagonist for 16 days. Beginning on day 5 of GnRH antagonist administration, subjects were administered estrogen (E(2)) for 11 days, and beginning on day 12 of GnRH antagonist administration, subjects added progesterone (E(2)-P(4)) for 4 days. On days 2, 9, and 16 of GnRH antagonist administration, we estimated ECFV (inulin washout), transcapillary escape rate of albumin (TER(alb)), and PV (Evans blue dye). Plasma E(2) concentration increased from 17.9 +/- 4.5 (GnRH antagonist) to 195.9 +/- 60.1 (E(2), P < 0.05) to 245.6 +/- 62.9 pg/ml (E(2)-P(4), P < 0.05). Compared with GnRH antagonist (1.3 +/- 0.5 ng/ml), plasma P(4) concentration was unchanged during E(2) (0.9 +/- 0.3 ng/ml) and increased to 9.4 +/- 3.1 ng/ml during E(2)-P(4) (P < 0.05). Both E(2) (44.1 +/- 3.1 ml/kg) and E(2)-P(4) (47.7 +/- 2.8 ml/kg) increased PV compared with GnRH antagonist (42.8 +/- 1.3 ml/kg, P < 0.05). Within-subjects TER(alb) was a strong negative predictor of PV (mean r = 0.92 +/- 0.03, P < 0.05), and TER(alb) was lowest during E(2)-P(4) (5.7 +/- 0.5, 4.1.0 +/- 1.1, and 2.8 +/- 0.9%/h, P < 0.05, for GnRH antagonist, E(2), and E(2)-P(4), respectively). ECFV was reduced during E(2) (227 +/- 31 ml/kg, P < 0.05) compared with both GnRH antagonist (291 +/- 37 ml/kg) and E(2)-P(4) (283 +/- 19 ml/kg). Thus the percentage of extracellular fluid in the plasma compartment increased to 21.0% (P < 0.05) during E(2) compared with GnRH antagonist (16.1%) and E(2)-P(4) (17.2%) administration. Thus E(2) increased PV via actions on the capillary endothelium to lower TER(alb) and favor intravascular water retention, whereas during E(2)-P(4) PV increased via the combined responses of ECFV expansion and lower TER(alb).     

Splenic denervation worsens lipopolysaccharide-induced hypotension, hemoconcentration, and hypovolemia

During lipopolysaccharide (LPS)-induced endotoxemia, increased intrasplenic fluid efflux contributes to a reduction in plasma volume. We hypothesized that splenic sympathetic nerve activity (SSNA), which increases during endotoxemia, limits intrasplenic fluid efflux. We reasoned that splenic denervation would exaggerate LPS-induced intrasplenic fluid efflux and worsen the hypotension, hemoconcentration, and hypovolemia. A nonlethal dose of LPS (150 microg x kg(-1) x h(-1) for 18 h) was infused into conscious male rats bearing transit time flow probes on the splenic artery and vein. Fluid efflux was estimated from the difference in splenic arterial inflow and venous outflow (A-V). LPS significantly increased the (A-V) flow differential (fluid efflux) in intact rats (saline -0.01 +/- 0.02 ml/min, n = 8 vs. LPS +0.21 +/- 0.06 ml/min, n = 8); this was exaggerated in splenic denervated rats (saline -0.03 +/- 0.01 ml/min, n = 7 vs. LPS +0.41 +/- 0.08 ml/min, n = 8). Splenic denervation also exacerbated the LPS-induced hypotension, hemoconcentration, and hypovolemia (peak fall in mean arterial pressure: denervated 19 +/- 3 mmHg, n = 10 vs. intact 12 +/- 1 mmHg, n = 8; peak rise in hematocrit: denervated 6.7 +/- 0.3%, n = 8 vs. intact 5.0 +/- 0.3%, n = 8; decrease in plasma volume at 90-min post-LPS infusion: denervated 1.08 +/- 0.15 ml/100 g body wt, n = 7 vs. intact 0.54 +/- 0.08 ml/100 g body wt, n = 8). The exaggerated LPS-induced hypovolemia associated with splenic denervation was mirrored in the rise in plasma renin activity (90 min post-LPS: denervated 11.5 +/- 0.8 ng x ml(-1) x h(-1), n = 9 vs. intact 6.6 +/- 0.7 ng x ml(-1) x h(-1), n = 8). These results are consistent with our proposal that SSNA normally limits LPS-induced intrasplenic fluid efflux.