Renin-Aldosterone System in Osmoregulatory Reactions of Healthy Subjects in Response to Desmopressin

Systemic regulation of osmotic and ionic homeostasis was studied in healthy male volunteers after oral administration of desmopressin. Endogenous secretion of the antidiuretic hormone was inhibited by a water load (WL, 2% of the body mass). Desmopressin exerted an antidiuretic effect. In addition, the WL portion excreted during 4 h decreased and the urine osmolality at peak diuresis increased with the absence of osmotically free water. At maximum diuresis, the ratio between concentrations of osmotically active substances in the urine and in the blood was high, which reflected an intense antidiuretic effect. Desmopressin progressively decreased the rate of sodium excretion owing to a change of sodium reabsorption in the kidneys. The WL increased the level of aldosterone and the activity of renin in blood plasma 1.5 h after its administration. Contrary to the control series, desmopressin stimulated the renin-angiotensin-aldosterone system only by the end of the 4-h observation period. A significant negative correlation between the aldosterone level and the rate of sodium excretion was observed 3 h after the beginning of testing (r = ?0.76). Thus, under conditions of water loading, desmopressin had a specific antidiuretic effect involving systemic mechanisms of ion regulation.     

Atrial natriuretic peptide in acute mountain sickness

To test the hypothesis that elevated atrial natriuretic peptide (ANP) may be involved in altered fluid homeostasis at high altitude, we examined 25 mountaineers at an altitude of 550 m and 6, 18, and 42 h after arrival at an altitude of 4,559 m, which was climbed in 24 h starting from 3,220 m. In 14 subjects, symptoms of acute mountain sickness (AMS) were absent or mild (group A), whereas 11 subjects had severe AMS (group B). Fluid intake was similar in both groups. In group B, urine flow decreased from 61 +/- 8 (base line) to 36 +/- 3 (SE) ml/h (maximal decrease) (P less than 0.05) and sodium excretion from 7.9 +/- 0.9 to 4.6 +/- 0.7) mmol.l-1.h-1 (P less than 0.05); ANP increased from 31 +/- 4 to 87 +/- 26 pmol/l (P less than 0.001), plasma aldosterone from 191 +/- 27 to 283 +/- 55 pmol/l (P less than 0.01 compared with group A), and antidiuretic hormone (ADH) from 1.0 +/- 0.1 to 2.9 +/- 1.2 pmol/l (P = 0.08 compared with group A). These variables did not change significantly in group A, with the exception of a decrease in plasma aldosterone from 189 +/- 19 to 111 +/- 17 pmol/l (P less than 0.01). There were no measurable effects of elevated ANP on natriuresis, cortisol, or blood pressure. The reduced diuresis in AMS may be explained by increased plasma aldosterone and ADH overriding the expected renal action of ANP. The significance of elevated ANP in AMS remains to be established.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiorenal-endocrine responses to head-out immersion at night

Cardiorenal-endocrine responses to 3-h head-out immersion (HOI) (water temperature = 34.5 +/- 0.5 degrees C) were studied during day (0900-1400 h) and night (2300-0400 h) in six hydropenic male human subjects. Although HOI induced a reversible increase in urine flow in all subjects, the response was faster and greater in magnitude during the day compared with night (P less than 0.05). Na excretion and osmolal clearance (Cosm) also followed the identical response pattern as urine flow, and in fact, the HOI-induced diuresis was entirely accounted for by the increased Cosm. Endogenous creatinine clearance was not different between the day and the night and remained unchanged during HOI. Both plasma renin activity and aldosterone concentration and urinary aldosterone excretion were nearly twofold greater during the day compared with night before HOI but decreased to the same level during HOI in both daytime and the nighttime series (P less than 0.05). There was no correlation between the Na excretion rate and renin-aldosterone levels either before or during HOI. Plasma antidiuretic hormone (ADH) level was comparable between day and night before HOI and decreased to a similar level during HOI in both daytime and nighttime series (P less than 0.05 for nighttime HOI). Cardiac output increased from 3.3 1/min before HOI to 5-6 1/min during HOI without showing any significant circadian difference. Hematocrit, hemoglobin, and plasma concentrations remained unchanged under all conditions. It is concluded that the renal response to HOI is subject to nocturnal inhibition, which cannot be attributed to circadian differences in the degree of HOI-induced central blood pooling, renin-aldosterone, or ADH responses.     

Antidiuretic activity of terlipressin (triglycyl-lysine vasopressin)--role of pressure natriuresis.

Terlipressin (triglycyl-lysine vasopressin TP), a "hormonogen" analogue, was introduced in gastroenterology for its low and protracted vasopressor action, reducing bleeding from gastrointestinal tract. Its antidiuretic activity, estimated originally in ethanol-anaesthetized rats (Sawyer's method) was claimed to be equally low and protracted. We performed several series of antidiuretic tests on conscious rats (Burn's method) with the following results. TP in low doses of 0.05-1.0 micrograms/kg exhibited typical dose-dependent antidiuretic effect. In the dose of 0.2 micrograms/kg, the dynamics of urine and sodium excretion did not differ from that after equivalent dose of lysine vasopressin and equipotent dose of DDAVP. The antidiuretic potency of TP (estimated by parallel line assay) was 175.0 U/mg. TP in doses of 5.0 and 20.0 micrograms/kg exhibited limited diuresis and marked natriuresis. High osmolality and sodium content were present in all portions of excreted urine. The discrepancy between previous and our results concerning antidiuretic activity of TP and the role of pressure natriuresis for overall renal action of TP are discussed.     

Endocrine concomitants of sweating and sweat depression

The effect of humid heat (Ta = 43 degrees C, Pa = 32 Torr) on sweat rate, plasma renin activity and plasma levels of aldosterone and antidiuretic hormone (ADH) was studied in four male subjects before and after repeated heat exposures. Over-sweating and sweat drippage followed by hidromeiosis were observed in three subjects during initial heat exposure. With repeated humid heat exposures increased sweat rates were accompanied by a more intense sweat depression (hidromeiosis) in all four subjects. In our conditions, no changes in plasma levels of aldosterone and ADH or plasma renin activity were observed with hidromeiosis. Plasma renin activity was slightly depressed by repeated exposures, whereas plasma volumes were enhanced, with no significant changes in plasma Na or K. The results suggest that neither ADH nor the components of the renin-angiotensin aldosterone system are involved in the hidromeiotic phenomenon.     

Effect of an antidiuretic hormone on the aldosterone level in the blood plasma of rats with chronic water load and limited sodium intake

The concentration of aldosterone in blood plasma of rats with chronic water and restricted sodium chloride intake substantially rose after subcutaneous injection of the antidiuretic hormone pituitrin in physiological doses. No simultaneous increase in blood corticosterone was seen. The production of hormones by rat adrenals remained unchanged. The results of experiments made with ACTH alone or combined with pituitrin permitted the conclusion that the increase in aldosterone concentration was not linked with a possible stimulation of endogenous ACTH secretion. The augmentation of aldosterone concentration in the peripheral blood of rats with chronic water intake induced by pituitrin is likely to be due to a decrease in metabolic clearance of the hormone.     

Effect of treatment with enalapril maleate on the levels of circulating catecholamines, beta endorphins, prostaglandins, and concentration of sodium in erythrocytes in patients with essential hypertension

An effect of enalapril maleate on the activity of renin-angiotensin-aldosterone system and sympathetic reactivity, erythrocyte prostaglandin and sodium levels as well as blood beta-endorphin was investigated in 28 patients with the essential arterial blood hypertension. It was found that enalapril maleate significantly increased plasma renin activity, decreased plasma norepinephrine and its 24-hour excretion, and decreased erythrocyte beta-endorphin and sodium levels. Blood epinephrine and aldosterone levels and their daily excretion remained unchanged similarly to prostaglandins. The above results suggest that a decrease in sympathetic system activity and intracellular sodium concentration may play a role in the hypotensive action of enalapril maleate related to the inhibition of angiotensin II formation.     

Renal effects of fresh water-induced hypo-osmolality in a marine adapted seal

With few exceptions, marine mammals are not exposed to fresh water; however quantifying the endocrine and renal responses of a marine-adapted mammal to the infusion of fresh water could provide insight on the evolutionary adaptation of kidney function and on the renal capabilities of these mammals. Therefore, renal function and hormonal changes associated with fresh water-induced diuresis were examined in four, fasting northern elephant seal ( Mirounga angustirostris) (NES) pups. A series of plasma samples and 24-h urine voids were collected prior to (control) and after the infusion of water. Water infusion resulted in an osmotic diuresis associated with an increase in glomerular filtration rate (GFR), but not an increase in free water clearance. The increase in excreted urea accounted for 96% of the increase in osmotic excretion. Following infusion of fresh water, plasma osmolality and renin activity decreased, while plasma aldosterone increased. Although primary regulators of aldosterone release (Na(+), K(+) and angiotensin II) were not significantly altered in the appropriate directions to individually stimulate aldosterone secretion, increased aldosterone may have resulted from multiple, non-significant changes acting in concert. Aldosterone release may also be hypersensitive to slight reductions in plasma Na(+), which may be an adaptive mechanism in a species not known to drink seawater. Excreted aldosterone and urea were correlated suggesting aldosterone may regulate urea excretion during hypo-osmotic conditions in NES pups. Urea excretion appears to be a significant mechanism by which NES pups sustain electrolyte resorption during conditions that can negatively affect ionic homeostasis such as prolonged fasting.     

Atrial natriuretic peptide is only a minor diuretic factor in dehydrated subjects immersed to the neck in water

To determine if the atrial natriuretic peptide (ANP) is an important factor for inducing diuresis during head-out water immersion even in dehydrated subjects, six healthy volunteers were immersed up to the neck in water at 34.5 degrees C for three hrs. Significant diuresis and natriuresis occurred, but urine osmolality decreased and negative CH2O was restored in a positive direction toward zero, even though subjects were still in a state of considerable dehydration. Plasma renin activity and plasma angiotensin I and II concentrations decreased but that of plasma aldosterone remained unchanged during water immersion, and plasma ANP did not increase throughout the examination. On the basis of the data of the present study, the factor inducing diuresis during head-out water immersion in hydrated subjects appears to differ from that in dehydrated subjects, and the main factor inducing diuresis during water immersion in dehydrated subjects may be the suppression of vasopressin release and not ANP.     

Lidocaine pharmacokinetics during water immersion in normal humans

Water immersion produces a marked diuresis, natriuresis, and kaliuresis in association with suppression of the renin-aldosterone system. These effects are mediated primarily by an increase in central blood volume. Consequently, this redistribution and the resultant marked increase in cardiac output is associated with alterations in the circulating levels of several volume regulatory hormones, including plasma renin activity and plasma aldosterone. Although the changes in these blood hormonal levels probably reflect perturbation of hormonal release, it is conceivable that the above-mentioned central hemodynamic modifications result in an altered splanchnic blood flow, thereby modulating hormonal clearances. We assessed the effects of immersion on hepatic blood flow by determining the pharmacokinetics of single doses of lidocaine administered intravenously. Seven normal male subjects were studied during a time-control period and during water immersion to the neck. The clearance of lidocaine was unaltered by immersion, suggesting that the presumed marked central hypervolemia and increased cardiac output was not associated with changes in splanchnic blood flow.     

Renal, cardiovascular and endocrine effects of centrally administered galanin in the anaesthetised rat.

Several studies implicate galanin as a central neuromodulator with an ability to influence hypothalamic and pituitary secretion. Central galanin content is also sensitive to the state of body hydration. Cardiovascular, renal and peripheral endocrine changes evoked by intracerebroventricular administration of galanin have been examined in the anaesthetized rat. Central galanin infusion consistently induced a transitory diuresis, the increase in urine flow being associated with a reduction in urine osmolality. There was no demonstrable change in plasma vasopressin concentration at the end of a 40 min galanin infusion. However, plasma aldosterone and corticosterone concentrations were significantly reduced by comparison with time-matched vehicle infused controls. There were no clear changes in renal electrolyte excretion or in heart rate or mean arterial blood pressure during the study period. The findings of this study support a participatory role for galanin in body fluid homeostasis, though the mechanisms responsible for mediating its central action on urine production remain unclear.     

Mechanism of the central effects of dopamine and metoclopramide on aldosterone regulation in the rat

To investigate the mechanism of the central action of dopamine and its antagonist, metoclopramide, on the regulation of aldosterone, studies were performed in 54 conscious rats with and without bilateral nephrectomy. In normal and sham-operated rats, intracerebroventricular injection of dopamine resulted in a significant suppression of plasma renin activity and plasma aldosterone at 30 min, and intracerebroventricular injection of metoclopramide resulted in a significant elevation of plasma renin activity and plasma aldosterone at 30 min without altering the plasma corticosterone and potassium levels. In bilaterally nephrectomized rats, the plasma renin activity was significantly reduced and it did not respond to dopamine or metoclopramide. In these rats, intracerebroventricular injection of metoclopramide exerted no effect on the plasma aldosterone, but intracerebroventricular injection of dopamine increased the plasma aldosterone slightly. However, this increase was not statistically significant. These findings suggest that the dopaminergic system in the brain is involved in the regulation of aldosterone secretion, mainly with changes in the peripheral renin-angiotensin axis in rats.     

Sleep deprivation induces excess diuresis and natriuresis in healthy children

Urine production is reduced at night, allowing undisturbed sleep. This study was undertaken to show the effect of sleep deprivation (SD) on urine production in healthy children. Special focus was on gender and children at an age where enuresis is still prominent. Twenty healthy children (10 girls) underwent two 24-h studies, randomly assigned to either sleep or SD on the first study night. Diet and fluid intake were standardized. Blood samples were drawn every 4 h during daytime and every 2 h at night. Urine was fractionally collected. Blood pressure and heart rate were noninvasively monitored. Blood was analyzed for plasma antidiuretic hormone (AVP), atrial natriuretic peptide (ANP), angiotensin II, aldosterone, and renin. Urine was analyzed for aquaporin-2 and PGE(2). Successful SD was achieved in all participants with a minimum of 4 h 50 min, and full-night SD was obtained in 50% of the participants. During SD, both boys and girls produced markedly larger amounts of urine than during normal sleep (477 ± 145 vs. 291 ± 86 ml, P < 0.01). SD increased urinary excretion of sodium (0.17 ± 0.05 vs. 0.10 ± 0.03 mmol·kg(-1)·h(-1)) whereas solute-free water reabsorption remained unchanged. SD induced a significant fall in nighttime plasma AVP (P < 0.01), renin (P < 0.05), angiotensin II (P < 0.001), and aldosterone (P < 0.05) whereas plasma ANP levels remained uninfluenced (P = 0.807). Nighttime blood pressure and heart rate were significantly higher during SD (mean arterial pressure: 78.5 ± 8.0 vs. 74.7 ± 8.7 mmHg, P < 0.001). SD leads to natriuresis and excess diuresis in healthy children. The underlying mechanism could be a reduced nighttime dip in blood pressure and a decrease in renin-angiotensin-aldosterone system levels during sleep deprivation.     

Role of ADH in ethylketocyclazocine-induced diuresis: studies in the Brattleboro rat

Kappa opioids produce diuresis presumably through ADH. We investigated further the role of ADH in kappa-induced diuresis by utilizing the Brattleboro rat, a strain lacking endogenous ADH. Ethylketocyclazocine (EKC), a kappa opioid prototype, increased urine formation in Sprague-Dawley, but not in Brattleboro rats. Furthermore, EKC pretreatment abolished the antidiuretic response to ADH administered exogenously to Brattleboro rats. Our study suggests that, in addition to a fall in plasma ADH reported previously, kappa opioids have direct effects on the renal response to ADH.     

Digoxin-like substance in blood and hypertension in dialysed patients with chronic renal failure]

Concentration of free serotonin, adrenaline, noradrenaline, aldosterone and plasma renin activity have been assayed in blood of 18 patients with the primary arterial hypertension (WHO stage I) and in 10 healthy volunteers. It was found that blood free serotonin and noradrenaline are increased in hypertensive patient. No difference in adrenaline and aldosterone levels and plasma renin activity was seen. No significant correlation between free serotonin and assayed hormones was noted.     

Renal function and pituitary hormone release during cerebral osmostimulation and TRH in dogs

The effects of increases in serum osmolality on renal function and plasma levels of radioimmunoassayable prolactin (PRL) and luteinizing hormone (LH) were examined during intracarotid (IC) infusions of hypertonic NaCl in conscious dogs with a sustained water diuresis (SWD). A 10 minute bilateral IC infusion of 45 μmole/kg·min·artery of NaCl during SWD which raised jugular osmolality by 10.1 mOsm/kg, without significantly altering peripheral venous osmolality, produced a significant decrease in free water clearance (C_H2O) at 20 to 40 minutes postinfusion. IC infusions of 0.9% NaCl did not produce an antidiuretic response. No change in heart rate or blood pressure from preinfusion control values occurred during NaCl infusions. Elevations in cerebral osmolality did not result in changes in circulating levels of LH or PRL which qualitatively differed from levels of these hormones recorded during IC infusions of 0.9% NaCl. Although fluctuations in levels of LH occurred during experiments, renal function was not concomitantly affected. The results suggest that a specificity exists in the hormonal response to selective elevations of cerebral osmolality. The administration of TRH 3.8–4.2 μg/kg produced a transient increase in blood pressure and inhibited a water diuresis, the latter possibly as a result of releasing antidiuretic hormone.     

Vasopressin inhibits diuresis induced by water immersion in humans.

We tested the hypothesis that 1-desamino-8-D-arginine vasopressin (DDAVP), a V2-receptor agonist, could inhibit the diuresis induced by water immersion in humans. Water and electrolyte excretion, plasma atrial natriuretic factor concentration, and plasma aldosterone concentration were measured initially and after 3 h of water immersion in 13 healthy sodium-replete men given either placebo or 20 micrograms of intranasal DDAVP. Guanosine 3',5'-cyclic monophosphate and urea excretion and urine osmolality were also determined. DDAVP inhibited the diuresis induced by water immersion in men: 758 +/- 168 (SE) ml/3 h in the placebo group vs. 159 +/- 28 ml/3 h in the DDAVP group (P less than 0.05). After 3 h of water immersion, plasma atrial natriuretic factor concentrations were increased from 11 +/- 2 to 20 +/- 4 pg/ml in the placebo group and from 14 +/- 2 to 33 +/- 4 pg/ml in the DDAVP group (P less than 0.05). Plasma aldosterone concentrations were decreased from 98 +/- 18 to 45 +/- 6 pg/ml in the placebo group (P less than 0.05) and from 54 +/- 17 to 25 +/- 5 pg/ml in the DDAVP group (P less than 0.05). Despite these changes in aldosterone and atrial natriuretic factor concentrations, which should increase sodium excretion, DDAVP decreased the natriuresis induced by water immersion in humans: 56 +/- 8 meq Na+/3 h in the placebo group vs. 36 +/- 6 meq Na+/3 h in the DDAVP group (P less than 0.05). DDAVP may be used to prevent the diuresis associated with central redistribution of blood volumes that occur during water immersion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resistance of 1-deamino-[8-D-arginine]-vasopressin to in vitro degradation as compared with arginine vasopressin

In order to elucidate the mechanism(s) responsible for the prolonged antidiuretic activity of 1-deamino-[8-D-arginine]-vasopressin (dDAVP), antidiuretic activities of dDAVP and arginine vasopressin (AVP) were determined in the rat following either oral administration or incubation with AVP-degrading enzymes and reagents. Oral administration of dDAVP to conscious water-loaded rats resulted in significant antidiuresis while AVP resulted in slight and transient antidiuresis. In the ethanol anesthetized water-loaded rats, antidiuretic activities of 136pg of AVP and 50pg of dDAVP, which were found to be equipotent, were compared after incubation with digestive enzymes (pepsin, trypsin, alpha-chymotrypsin), late pregnancy plasma, or sodium thioglycollate. The antidiuretic activity of AVP was completely destroyed by 30-min incubation with trypsin, alpha-chymotrypsin, or late pregnancy plasma and almost all AVP was inactivated by 0.2 M sodium thioglycollate. On the other hand, the antidiuretic activity of dDAVP was not destroyed by trypsin or pregnancy plasma but was partly destroyed by alpha-chymotrypsin and sodium thioglycollate. Neither the antidiuretic activity of AVP nor that of dDAVP was affected by pepsin. Thus, the antidiuresis observed after oral administration of dDAVP might be brought about by the resistance to digestive enzymes. Furthermore, the resistance of dDAVP to digestive enzymes, late pregnancy plasma and sodium thioglycollate might be responsible for the prolonged antidiuretic action of dDAVP in vivo.     

Effects of desmopressin on prolonging survival in stable hypothermia in rats

The aim of the present study was to examine whether minimizing plasma volume loss due to cold-induced diuresis can increase the survival time of rats maintained in long-term stable hypothermia (~24 h at a body temperature of 19 degrees C). Infusion of desmopressin (0.5-2.0 microg), a potent antidiuretic agent, during the cooling period enhanced survival over saline controls in a dose-related manner. The enhanced survival was accompanied by a significant delay in the expected increase of hematocrit and decrease of plasma volume as compared with those seen in saline controls. In contrast, treating the rats with the same dose range of another vasopressin analog, [beta-mercapto-beta,beta-cyclopentamethyl enepropionyl]-vasopressin, which has no antidiuretic action, failed to enhance survival over saline control. Further, treating the rats with the optimal dose of desmopressin (1 microg) at the later stage of hypothermia failed to elicit any beneficial effect. Our results indicate that by using desmopressin early during the cooling phase of the hypothermia, plasma volume and rheological parameters important for sustaining microcirculation can be better maintained than those seen in saline controls. These improvements may have contributed to the observed longer survival time in hypothermia.     

Species differences in the effect of decreased CSF sodium concentration on salt appetite

During the course of evolution from the beginning of the Caenozoic period, the mammalian species have irradiated into increasingly diverse environments and these physical conditions have imposed powerful selection pressures on the systems of water and salt homeostasis. In the case of physiological actions of hormonal elements of the control systems, effects of antidiuretic hormone and aldosterone on water and salt conservation and of renin-angiotensin II on blood pressure and aldosterone secretion show a general similarity across mammalian species. However, evidence is accruing that there may be large species variation in the vectors of physical, chemical and hormonal changes of the milieu which cause water and salt intake. In the sheep, physiological degree of reduction of CSF [Na] produced by IVT infusion of various hypertonic or isotonic saccharide solutions has a powerful stimulating effect on salt appetite of both Na replete and Na deficient animals. Increasing CSF [Na] reduces appetite. The 0.7 M mannitol CSF infusions initially stimulated thirst but eventually depressed it, presumably due to reduction of CSF [Na]. By contrast, in wild rabbits infusion of 0.9 M mannitol CSF for 2 days at 17 microliter/h caused a large reduction of water intake, a diuresis and no significant increase in salt intake. In laboratory white rats, 0.7 M mannitol CSF infusion at 10 microliter/h for 4 days by Alzet pump, did not increase salt appetite though the infusion was calculated to produce moderate reduction of CSF [Na]. It would appear that there may be significant species differences in effect of reduced CSF [Na] on salt appetite.