Systemic vascular resistance during brief withdrawal of angiotensin converting enzyme inhibition in heart failure.

We tested the hypothesis that moderate increases in endogenous angiotensin II (Ang II) concentrations, induced by withdrawal of angiotensin converting enzyme inhibition (ACE-I) in patients with compensated heart failure (HF) on chronic medical therapy, do not increase or impair control of systemic vascular resistance (SVR). SVR was determined in supine and seated positions in 12 HF patients [NYHA class II-III; ejection fraction=0.29 +/- 0.03 (mean +/- SE)] and 9 control subjects. HF patients were investigated during high (n=11; withdrawal of ACE-I treatment for 24 h) and low (n=9; sustained ACE-I therapy) endogenous plasma Ang II concentrations. Withdrawal of ACE-I therapy in HF caused moderately increased Ang II concentrations of 30 +/- 5 pg/ml compared with 12 +/- 2 pg/ml in controls (p<0.05 vs. HF patients). Despite this, SVR was similar in HF (supine: 1503 +/- 159; seated: 1957 +/- 262 dyn s/cm5, p<0.05 vs. supine) and controls (supine: 1438 +/- 104; seated: 1847 +/- 127 dyn s/cm5, p<0.05 vs. supine). During sustained ACE-I therapy in HF, plasma Ang II concentrations were lower (6 +/- 2pg/ml, p<0.05 vs. withdrawal of ACE-I in HF) with no effect on supine SVR. However, the posture-induced increase in SVR in response to the seated position was attenuated. In conclusion, brief moderate increases in circulating plasma Ang II concentrations in compensated HF do not increase SVR compared to control subjects or impair control of SVR in response to a posture change.

Atrial distension, haemodilution, and acute control of renin release during water immersion in humans.

We tested the hypothesis that atrial distension (stimulation of cardiopulmonary baroreceptors) is not the single pivotal stimulus for the acute suppression of renin release during water immersion in humans and that immersion-induced haemodilution constitutes an important additional stimulus. In nine healthy male subjects, identical increases in atrial distension were induced by two immersion procedures (of 30 min each); one without (WI) and one with attenuation (WI + cuff) of the concomitant haemodilution (estimated from changes in plasma protein concentration) by inflating thigh cuffs during immersion. During WI, central venous pressure (CVP) and left atrial diameter (LAD) increased (P < 0.05) by 5.5 +/- 0.4 mmHg and 4.6 +/- 0.5 mm, respectively, and plasma protein concentration and plasma renin activity (PRA) progressively decreased (P < 0.05) by 4.8 +/- 0.5 g L(-1) and 1.6 +/- 0.2 ng mL(-1) h(-1) (to 49 +/- 4% of baseline values), respectively. The WI + cuff caused similar atrial distension as WI (CVP and LAD increased by 6.9 +/- 0.5 mmHg and 5.5 +/- 0.5 mm, respectively), attenuated haemodilution (plasma protein concentration decreased by 1.9 +/- 0.4 g L(-1), P < 0.05 vs. WI), and markedly inhibited suppression of PRA, which decreased by 0.4 +/- 0.1 ng mL(-1) h(-1) (to 87 +/- 4% of baseline values, P < 0.05 vs. WI). Differences in renin release could not be accounted for by differences in mean arterial pressure. In conclusion, baroreceptor stimulation induced by atrial distension is not the single pivotal stimulus for the acute suppression of renin release in response to intravascular volume expansion by water immersion in humans. Haemodilution constitutes a significant and conceivably the principal stimulus for the acute immersion-induced suppression of renin-angiotensin system activity.

Atrial distension, arterial pulsation, and vasopressin release during negative pressure breathing in humans.

During an antiorthostatic posture change, left atrial (LA) diameter and arterial pulse pressure (PP) increase, and plasma arginine vasopressin (AVP) is suppressed. By comparing the effects of a 15-min posture change from seated to supine with those of 15-min seated negative pressure breathing in eight healthy males, we tested the hypothesis that with similar increases in LA diameter, suppression of AVP release is dependent on the degree of increase in PP. LA diameter increased similarly during the posture change and negative pressure breathing (-9 to -24 mmHg) from between 30 and 31 +/- 1 to 34 +/- 1 mm (P < 0.05). The increase in PP from 38 +/- 2 to 44 +/- 2 mmHg (P < 0.05) was sustained during the posture change but only increased during the initial 5 min of negative pressure breathing from 36 +/- 3 to 42 +/- 3 mmHg (P < 0.05). Aortic transmural pressure decreased during the posture change and increased during negative pressure breathing. Plasma AVP was suppressed to a lower value during the posture change (from 1.5 +/- 0.3 to 1.2 +/- 0.2 pg/ml, P < 0.05) than during negative pressure breathing (from 1.5 +/- 0.3 to 1.4 +/- 0.3 pg/ml). Plasma norepinephrine was decreased similarly during the posture change and negative pressure breathing compared with seated control. In conclusion, the results are in compliance with the hypothesis that during maneuvers with similar cardiac distension, suppression of AVP release is dependent on the increase in PP and, furthermore, probably unaffected by static aortic baroreceptor stimulation.

Central volume expansion is pivotal for sustained decrease in heart rate during seated to supine posture change.

During prolonged, static carotid baroreceptor stimulation by neck suction (NS) in seated humans, heart rate (HR) decreases acutely and thereafter gradually increases. This increase has been explained by carotid baroreceptor adaptation and/or buffering by aortic reflexes. During a posture change from seated to supine (Sup) with similar carotid stimulation, however, the decrease in HR is sustained. To investigate whether this discrepancy is caused by changes in central blood volume, we compared (n = 10 subjects) the effects of 10 min of seated NS (adjusted to simulate carotid stimulation of a posture change), a posture change from seated to Sup, and the same posture change with left atrial (LA) diameter maintained unchanged by lower body negative pressure (Sup + LBNP). During Sup, the prompt decreases in HR and mean arterial pressure (MAP) were sustained. HR decreased similarly within 30 s of NS (65 +/- 2 to 59 +/- 2 beats/min) and Sup + LBNP (65 +/- 2 to 58 +/- 2 beats/min) and thereafter gradually increased to values of seated. MAP decreased similarly within 5 min during Sup + LBNP and NS (by 7 +/- 1 to 9 +/- 1 mmHg) and thereafter tended to increase toward values of seated subjects. Arterial pulse pressure was increased the most by Sup, less so by Sup + LBNP, and was unchanged by NS. LA diameter was only increased by Sup. In conclusion, static carotid baroreceptor stimulation per se causes the acute (<30 s) decrease in HR during a posture change from seated to Sup, whereas the central volume expansion (increased LA diameter and/or arterial pulse pressure) is pivotal to sustain this decrease. Thus the effects of central volume expansion override adaptation of the carotid baroreceptors and/or buffering of aortic reflexes.

Neuroendocrine and renal effects of intravascular volume expansion in compensated heart failure.

To examine if the neuroendocrine link between volume sensing and renal function is preserved in compensated chronic heart failure [HF, ejection fraction 0.29 +/- 0.03 (mean +/- SE)] we tested the hypothesis that intravascular and central blood volume expansion by 3 h of water immersion (WI) elicits a natriuresis. In HF, WI suppressed ANG II and aldosterone (Aldo) concentrations, increased the release of atrial natriuretic peptide (ANP), and elicited a natriuresis (P < 0.05 for all) compared with seated control. Compared with control subjects (n = 9), ANG II, Aldo, and ANP concentrations were increased (P < 0.05) in HF, whereas absolute and fractional sodium excretion rates were attenuated [47 +/- 16 vs. 88 +/- 15 micromol/min and 0.42 +/- 0.18 vs. 0.68 +/- 0.12% (mean +/- SE), respectively, both P < 0.05]. When ANG II and Aldo concentrations were further suppressed (P < 0.05) during WI in HF (by sustained angiotensin-converting enzyme inhibitor therapy, n = 9) absolute and fractional sodium excretion increased (P < 0.05) to the level of control subjects (108 +/- 34 micromol/min and 0.70 +/- 0.23%, respectively). Renal free water clearance increased during WI in control subjects but not in HF, albeit plasma vasopressin concentrations were similar in the two groups. In conclusion, the neuroendocrine link between volume sensing and renal sodium excretion is preserved in compensated HF. The natriuresis of WI is, however, modulated by the prevailing ANG II and Aldo concentrations. In contrast, renal free water clearance is attenuated in response to volume expansion in compensated HF despite normalized plasma AVP concentrations.

Mechanisms of hypotensive effects of a posture change from seated to supine in humans.

The hypothesis tested was that the hydrostatic stimulation of carotid baroreceptors is pivotal to decrease mean arterial pressure at heart level during a posture change from seated to supine. In eight males, the cardiovascular responses to a 15-min posture change from seated to supine were compared with those of water immersion to the xiphoid process and to the neck, respectively. Left atrial diameter and cardiac output (rebreathing) increased similarly during the posture change and water immersion to the xiphoid process and further so during neck immersion. Mean arterial pressure decreased by 12 +/- 2 mmHg during the posture change, by 5 +/- 1 mmHg during xiphoid immersion, and was unchanged during neck immersion. Arterial pulse pressure increased by 12 +/- 3 mmHg during the posture change (P < 0.05) and less during xiphoid and neck immersion by 7 +/- 3 mmHg (P < 0.05). Total peripheral vascular resistance decreased similarly during the posture change and neck immersion and slightly less during xiphoid immersion (P < 0.05). In conclusion, the hydrostatic stimulation of carotid baroreceptors combined with some additional increase in arterial pulse pressure, which also stimulates aortic baroreceptors, accounts for more than half of the hypotensive response at heart level to a posture change from seated to supine.

Cardiovascular effects of static carotid baroreceptor stimulation during water immersion in humans.

We hypothesized that the more-pronounced hypotensive and bradycardic effects of an antiorthostatic posture change from seated to supine than water immersion are caused by hydrostatic carotid baroreceptor stimulation. Ten seated healthy males underwent five interventions of 15-min each of 1) posture change to supine, 2) seated water immersion to the Xiphoid process (WI), 3) seated neck suction (NS), 4) WI with simultaneous neck suction (-22 mmHg) adjusted to simulate the carotid hydrostatic pressure increase during supine (WI + NS), and 5) seated control. Left atrial diameter increased similarly during supine, WI + NS, and WI and was unchanged during control and NS. Mean arterial pressure (MAP) decreased the most during supine (7 +/- 1 mmHg, P < 0.05) and less during WI + NS (4 +/- 1 mmHg) and NS (3 +/- 1 mmHg). The decrease in heart rate (HR) by 13 +/- 1 beats/min (P < 0.05) and the increase in arterial pulse pressure (PP) by 17 +/- 4 mmHg (P < 0.05) during supine was more pronounced (P < 0.05) than during WI + NS (10 +/- 2 beats/min and 7 +/- 2 mmHg, respectively) and WI (8 +/- 2 beats/min and 6 +/- 1 mmHg, respectively, P < 0.05). Plasma vasopressin decreased only during supine and WI, and plasma norepinephrine, in addition, decreased during WI + NS (P < 0.05). In conclusion, WI + NS is not sufficient to decrease MAP and HR to a similar extent as a 15-min seated to supine posture change. We suggest that not only static carotid baroreceptor stimulation but also the increase in PP combined with low-pressure receptor stimulation is a possible mechanism for the more-pronounced decrease in MAP and HR during the posture change.

Cardiovascular and neuroendocrine responses to left lateral position in non-obese young males.

Previous results from our laboratory indicate that the heart is distended by the left lateral position (LAT) compared to horizontal supine (SUP). We therefore tested the hypothesis that cardiac output is increased by LAT and that mean arterial pressure is maintained unchanged or even decreased through peripheral vasodilatation induced by cardiopulmonary low-pressure receptor stimulation. Twelve non-obese young males were investigated. The location of the mid-aorta between the aortic valves was used as the hydrostatic reference point for the arterial pressure measurements. It was determined by magnetic resonance (n=6) to be 7.0 +/- 0.2 cm below the sternum in SUP (1/3 of anteroposterior chest diameter below the sternum) and 2.5 +/- 0.2 cm below the midsternal level in LAT. Brachial mean (auscultation) and finger mean arterial pressures (infrared photoplethysmography), cardiac output (foreign gas rebreathing), heart rate, and plasma concentrations (n=6) of vasoactive hormones were unchanged by LAT. In conclusion, cardiac output, mean arterial pressures, and vasoactive hormone releases were unaffected by 30 min of LAT. Furthermore, the hydrostatic reference points for arterial pressure measurements is located one third of the antero-posterior chest diameter below the sternum in SUP and 2.5 cm below the midsternal level in LAT in non-obese young males.

Cardiovascular and neuroendocrine responses to water immersion in compensated heart failure.

The hypothesis was tested that cardiovascular and neuroendocrine (norepinephrine, renin, and vasopressin) responses to central blood volume expansion are blunted in compensated heart failure (HF). Nine HF patients [New York Heart Association class II-III, ejection fraction = 0.28 +/- 0.02 (SE)] and 10 age-matched controls (ejection fraction = 0.68 +/- 0.03) underwent 30 min of thermoneutral (34.7 +/- 0.02 degrees C) water immersion (WI) to the xiphoid process. WI increased (P < 0.05) central venous pressure by 3.7 +/- 0.6 and 3.2 +/- 0.4 mmHg and stroke volume index by 12.2 +/- 2.1 and 7.2 +/- 2.1 ml. beat(-1). m(-2) in controls and HF patients, respectively. During WI, systemic vascular resistance decreased (P < 0.05) similarly by 365 +/- 66 and 582 +/- 227 dyn. s. cm(-5) in controls and HF patients, respectively. Forearm subcutaneous vascular resistance decreased by 19 +/- 7% (P < 0.05) in controls but did not change in HF patients. Heart rate decreased less during WI in HF patients, whereas release of norepinephrine, renin, and vasopressin was suppressed similarly in the two groups. We suggest that reflex control of forearm vascular beds and heart rate is blunted in compensated HF but that baroreflex-mediated systemic vasodilatation and neuroendocrine responses to central blood volume expansion are preserved.

Low LBNP tolerance in men is associated with attenuated activation of the renin-angiotensin system.

Plasma vasoactive hormone concentrations [epinephrine (p(Epi)), norepinephrine (p(NE)), ANG II (p(ANG II)), vasopressin (p(VP)), endothelin-1 (p(ET-1))] and plasma renin activity (p(RA)) were measured periodically and compared during lower body negative pressure (LBNP) to test the hypothesis that responsiveness of the renin-angiotensin system, the latter being one of the most powerful vasoconstrictors in the body, is of major importance for LBNP tolerance. Healthy men on a controlled diet (2,822 cal/day, 2 mmol. kg(-1). day(-1) Na(+)) were exposed to 30 min of LBNP from -15 to -50 mmHg. LBNP was uneventful for seven men [25 +/- 2 yr, high-tolerance (HiTol) group], but eight men (26 +/- 3 yr) reached presyncope after 11 +/- 1 min [P < 0.001, low-tolerance (LoTol) group]. Mean arterial pressure (MAP) did not change measurably, but central venous pressure and left atrial diameter decreased similarly in both groups (5-6 mmHg, by approximately 30%, P < 0.05). Control (0 mmHg LBNP) hormone concentrations were similar between groups, however, p(RA) differed between them (LoTol 0.6 +/- 0.1, HiTol 1.2 +/- 0.1 ng ANG I. ml(-1). h(-1), P < 0.05). LBNP increased (P < 0. 05) p(RA) and p(ANG II), respectively, more in the HiTol group (9.9 +/- 2.2 ng ANG I. ml(-1). h(-1) and 58 +/- 12 pg/ml) than in LoTol subjects (4.3 +/- 0.9 ng ANG I. ml(-1). h(-1) and 28 +/- 6 pg/ml). In contrast, the increase in p(VP) was higher (P < 0.05) in the LoTol than in the HiTol group. The increases (P < 0.05) for p(NE) were nonsignificant between groups, and p(ET-1) remained unchanged. Thus there may be a causal relationship between attenuated activation of p(RA) and p(ANG II) and presyncope, with p(VP) being a possible cofactor. Measurement of resting p(RA) may be of predictive value for those with lower hypotensive tolerance.

Does gender influence human cardiovascular and renal responses to water immersion?

We hypothesized that women and men exhibit similar cardiovascular and renal responses to thermoneutral water immersion (WI) to the neck. Ten women and nine men underwent two sessions in random order: 1) seated nonimmersed for 5.5 h (control) and 2) WI for 3 h, with subjects seated nonimmersed for 1.5 h pre- and 1 h postimmersion. We measured left atrial diameter, heart rate, arterial pressure, urine volume and osmolality, and urinary endothelin, urodilatin, sodium, and potassium excretion. No significant difference existed between groups in cardiovascular responses. The groups also exhibited mostly similar renal responses to immersion after adjustment for body mass. However, female urodilatin excretion per kilogram during immersion was over twofold that of men, and the female kaliuretic response to immersion was delayed and less pronounced relative to that in men. Men may excrete more potassium than women during immersion because men possess greater lean body mass (potassium per kilogram). Results obtained in men during WI may be cautiously extrapolated to women, yet urodilatin and potassium responses exhibit gender differences.

Forearm vascular and neuroendocrine responses to graded water immersion in humans.

The hypothesis that graded expansion of central blood volume by water immersion to the xiphoid process and neck would elicit a graded decrease in forearm vascular resistance was tested. Central venous pressure increased (P < 0.05) by 4.2 +/- 0.4 mmHg (mean +/- SEM) during xiphoid immersion and by 10.4 +/- 0.5 mmHg during neck immersion. Plasma noradrenaline was gradually suppressed (P < 0.05) by 62 +/- 8 and 104 +/- 11 pg mL-1 during xiphoid and neck immersion, respectively, indicating a graded suppression of sympathetic nervous activity. Plasma concentrations of arginine vasopressin were suppressed by 1.5 +/- 0.5 pg mL-1 (P < 0.05) during xiphoid immersion and by 2.0 +/- 0.5 pg mL-1 during neck immersion (P < 0.05 vs. xiphoid immersion). Forearm subcutaneous vascular resistance decreased to the same extent by 26 +/- 9 and 28 +/- 4% (P < 0.05), respectively, during both immersion procedures, whereas forearm skeletal muscle vascular resistance declined only during neck immersion by 27 +/- 6% (P < 0.05). In conclusion, graded central blood volume expansion initiated a graded decrease in sympathetic nervous activity and AVP-release. Changes in forearm subcutaneous vascular resistance, however, were not related to the gradual withdrawal of the sympathetic and neuroendocrine vasoconstrictor activity. Forearm skeletal muscle vasodilatation exhibited a more graded response with a detectable decrease only during immersion to the neck. Therefore, the forearm subcutaneous vasodilator response reaches saturation at a lower degree of central volume expansion than that of forearm skeletal muscle.

Arterial pulse pressure and vasopressin release during graded water immersion in humans.

Previous results indicate that arterial pulse pressure modulates release of arginine vasopressin (AVP) in humans. The hypothesis was therefore tested that an increase in arterial pulse pressure is the stimulus for suppression of AVP release during central blood volume expansion by water immersion. A two-step immersion model (n = 8) to the xiphoid process and neck, respectively, was used to attain two different levels of augmented cardiac distension. Left atrial diameter (echocardiography) increased from 28 +/- 1 to 34 +/- 1 mm (P < 0.05) during immersion to the xiphoid process and more so (P < 0.05), to 36 +/- 1 mm, during immersion to the neck. During immersion to the xiphoid process, arterial pulse pressure (invasively measured in a brachial artery) increased (P < 0.05) from 44 +/- 1 to 51 +/- 2 mmHg and to the same extent from 42 +/- 1 to 52 +/- 2 mmHg during immersion to the neck. Mean arterial pressure was unchanged during immersion to the xiphoid process and increased during immersion to the neck by 7 +/- 1 mmHg (P < 0.05). Arterial plasma AVP decreased from 2.5 +/- 0.7 to 1.8 +/- 0.5 pg/ml (P < 0. 05) during immersion to the xiphoid process and significantly more so (P < 0.05), to 1.4 +/- 0.5 pg/ml, during immersion to the neck. In conclusion, other factors besides the increase in arterial pulse pressure must have participated in the graded suppression of AVP release, comparing immersion to the xiphoid process with immersion to the neck. We suggest that when arterial pulse pressure is increased, graded distension of cardiopulmonary receptors modulate AVP release.

Arterial pressure in humans during weightlessness induced by parabolic flights.

Results from our laboratory have indicated that, compared with those of the 1-G supine (Sup) position, left atrial diameter (LAD) and transmural central venous pressure increase in humans during weightlessness (0 G) induced by parabolic flights (R. Videbaek and P. Norsk. J. Appl. Physiol. 83: 1862-1866, 1997). Therefore, because cardiopulmonary low-pressure receptors are stimulated during 0 G, the hypothesis was tested that mean arterial pressure (MAP) in humans decreases during 0 G to values below those of the 1-G Sup condition. When the subjects were Sup, 0 G induced a decrease in MAP from 93 +/- 4 to 88 +/- 4 mmHg (P < 0.001), and LAD increased from 30 +/- 1 to 33 +/- 1 mm (P < 0.001). In the seated position, MAP also decreased from 93 +/- 6 to 87 +/- 5 mmHg (P < 0.01) and LAD increased from 28 +/- 1 to 32 +/- 1 mm (P < 0.001). During 1-G conditions with subjects in the horizontal left lateral position, LAD increased compared with that of Sup (P < 0.001) with no further effects of 0 G. In conclusion, MAP decreases during short-term weightlessness to below that of 1-G Sup simultaneously with an increase in LAD. Therefore, distension of the heart and associated central vessels during 0 G might induce the hypotensive effects through peripheral vasodilatation. Furthermore, the left lateral position in humans could constitute a simulation model of weightlessness.

Contribution of the leg vasculature to hypotensive effects of an antiorthostatic posture change in humans.

1. Previous results from our laboratory have shown that vasodilatation in the legs prevents mean arterial pressure (MAP) from increasing during water immersion. Therefore, we tested the hypothesis that vasodilatation in the legs is necessary for the hypotensive effects to occur during a moderate antiorthostatic posture change. 2. Ten healthy males underwent a 5 min posture change from upright seated to horizontal supine (SUP) and back to seated again with (OCCL-SUP) and without simultaneous total arterial (154 +/- 1 mmHg) thigh occlusion, and a control seated period, also with and without arterial occlusion. Cardiac output (CO) was measured by a non-invasive foreign (N2O) gas rebreathing technique. 3. MAP (brachial auscultation) decreased during SUP from 94 +/- 3 to 84 +/- 2 mmHg (P < 0.0001) and total peripheral vascular resistance (TPR = MAP/CO, n = 8) decreased by 15 +/- 4 % (P < 0.001). During OCCL-SUP, MAP decreased from 98 +/- 2 to 90 +/- 2 mmHg (P < 0.005) and TPR decreased by 14 +/- 3 % (P < 0.01). 4. In conclusion, vasodilatation in the legs is not necessary for the decrease in MAP to occur during a moderate antiorthostatic manoeuvre. Therefore, vasodilatation in more central vascular beds (e.g. abdomen) can alone account for the hypotensive effects.

Mechanisms of inhibition of vasopressin release during moderate antiorthostatic posture change in humans.

The hypothesis was tested that the carotid baroreceptor stimulation caused by a posture change from upright seated with legs horizontal (Seat) to supine (Sup) participates in the suppression of arginine vasopressin (AVP) release. Ten healthy males underwent this posture change for 30 min without or with simultaneous application of lower body negative pressure (LBNP) adjusted to maintain left atrial diameter (LAD) at the Seat level. Throughout Sup, mean arterial pressure and heart rate decreased from 98 +/- 2 to 91 +/- 2 mmHg and from 63 +/- 2 to 55 +/- 2 beats/min (P < 0.05), respectively, whereas the corresponding decreases during Sup + LBNP were attenuated and of shorter duration (98 +/- 2 to 93 +/- 2 mmHg and 62 +/- 2 to 58 +/- 3 beats/min, P < 0.05). During Sup, LAD increased from 30 +/- 1 to 33 +/- 1 mm, and arterial pulse pressure (PP) increased from 40 +/- 2 to 47 +/- 2 mmHg, whereas plasma AVP decreased from 0.9 +/- 0.2 to 0.5 +/- 0.1 pg/ml (P < 0.05), and plasma norepinephrine (NE) decreased from 176 +/- 20 to 125 +/- 16 pg/ml (P < 0.05). During Sup + LBNP, there were no changes in LAD, PP, plasma AVP, or NE. In conclusion, vasopressin secretion is suppressed during an antiorthostatic posture change, which increases carotid sinus pressure, PP, and LAD. The suppression is absent when PP and LAD are prevented from increasing and is thus critically dependent on at least one of these stimuli.

Preventing hemodilution abolishes natriuresis of water immersion in humans.

The hypothesis was tested that hemodilution is one of the determinants of the water immersion (WI)-induced natriuresis. Eight males were subjected to 3 h of 1) WI to the midchest (Chest), 2) WI to the neck combined with thigh cuff-induced (80 mmHg) venous stasis (Neck + stasis), and 3) a seated time control (n = 6). Central venous pressure and left atrial diameter increased to the same extent during Chest and Neck + stasis (P < 0.05), whereas renal sodium excretion only increased during Chest from 77 +/- 7 to 225 +/- 13 micromol/min (P < 0.05). During Chest, plasma colloid osmotic pressure (COP) decreased from 27.7 +/- 0.7 to 25.1 +/- 0.7 mmHg (P < 0.05), and plasma volume (PV) increased from 3,263 +/- 129 to 3,581 +/- 159 ml (P < 0.05), whereas these variables remained unchanged during Neck + stasis. Plasma norepinephrine concentration decreased similarly during Chest and Neck + stasis by 45 +/- 7 and 34 +/- 4%, respectively (P < 0.05), whereas plasma renin activity decreased only during Chest (P < 0.05). In conclusion, during WI in humans 1) hemodilution (decrease in COP and increase in PV) is a pivotal stimulus for the natriuresis and 2) central blood volume expansion without hemodilution does not augment renal sodium output.

Vasopressin, angiotensin II and renal responses during water immersion in hydrated humans.

1. The hypothesis was tested that in hydrated humans the release of arginine vasopressin and angiotensin II is suppressed by water immersion (WI) and that this is a mechanism of the immersion-induced diuresis and natriuresis. Seven male subjects on controlled sodium (65-75 mmol per 24 h for 4 days) and water intake were studied. 2. Plasma vasopressin was promptly suppressed by WI, declining from 0. 76 +/- 0.13 to 0.23 +/- 0.08 pg ml-1 (P < 0.05), with a concomitant increase in renal water output (CH2O) from -0.4 +/- 0.2 to 4.4 +/- 0.7 ml min-1 (P < 0.05). Subsequently, CH2O returned to the level of control, whereas plasma vasopressin remained suppressed. Plasma osmolality gradually increased from 285 +/- 1 to 289 +/- 1 mosmol kg-1 (P < 0.05). WI caused a 9-fold increase in renal sodium excretion. Plasma angiotensin II decreased from 27.1 +/- 5.3 to 4.3 +/- 0.7 pg ml-1 (P < 0.05), and the intraindividual correlation coefficients between sodium excretion rates and angiotensin II concentrations varied between 0.73 and 0.96 (P < 0.002). 3. The data demonstrate that plasma vasopressin and angiotensin II concentrations decrease during WI in hydrated humans, concomitantly with initial increases in CH2O and sodium excretion. Therefore, vasopressin could constitute a mediator of CH2O and angiotensin II of the natriuresis of WI. The subsequent return of CH2O to the level of control is, however, also caused by other factors.

Contribution of abdomen and legs to central blood volume expansion in humans during immersion.

The hypothesis was tested that the abdominal area constitutes an important reservoir for central blood volume expansion (CBVE) during water immersion in humans. Six men underwent 1) water immersion for 30 min (WI), 2) water immersion for 30 min with thigh cuff inflation (250 mmHg) during initial 15 min to exclude legs from contributing to CBVE (WI+Occl), and 3) a seated nonimmersed control with 15 min of thigh cuff inflation (Occl). Plasma protein concentration and hematocrit decreased from 68 +/- 1 to 64 +/- 1 g/l and from 46.7 +/- 0.3 to 45.5 +/- 0.4% (P < 0.05), respectively, during WI but were unchanged during WI+Occl. Left atrial diameter increased from 27 +/- 2 to 36 +/- 1 mm (P < 0.05) during WI and increased similarly during WI+Occl from 27 +/- 2 to 35 +/- 1 mm (P < 0.05). Central venous pressure increased from -3.7 +/- 1.0 to 10.4 +/- 0.8 mmHg during WI (P < 0.05) but only increased to 7.0 +/- 0.8 mmHg during WI+Occl (P < 0.05). In conclusion, the dilution of blood induced by WI to the neck is caused by fluid from the legs, whereas the CBVE is caused mainly by blood from the abdomen.

Left atrial distension and antiorthostatic decrease in arterial pressure and heart rate in humans.

It was investigated to what degree left atrial distension augments the hypotensive effects of a 15-min moderate antiorthostatic maneuver in humans. Ten healthy males underwent a posture change from upright seated (Seat, legs horizontal) to supine (Sup) or to supine with simultaneous lower body negative pressure (Sup + LBNP) to keep left atrial diameter (LAD) unchanged. After 2.5 min of Sup, mean arterial pressure (MAP) decreased from 94 +/- 3 to 86 +/- 3 mmHg (P < 0.05), whereas a similar decrease was delayed 7.5 min into Sup + LBNP. Heart rate (HR) decreased within 2.5 min of Sup from 68 +/- 2 to 60 +/- 3 beats/min (P < 0.05) and remained significantly decreased for at least 2.5 min longer than during Sup + LBNP. Aortic systolic distension (ASD) increased by 59 +/- 17% during Sup (P < 0.05) but was unchanged during Sup + LBNP. The 29 +/- 4% decrease in plasma norepinephrine (NE) during Sup (P < 0.05) was abolished during Sup + LBNP. In conclusion, the increases in LAD and ASD seem important stimuli for the prompt decrease in MAP, the 2.5-min longer-lasting decrease in HR, and the sustained decrease in NE during a 15-min moderate antiorthostatic posture change in humans.