Mechanism of Antidiuretic Effect of Beta Adrenergic Stimulation

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A B S T R A C T The present study was undertaken to examine whether the beta adrenergic agonist, isoproterenol, increases plasma renin activity (PRA) by activation of intrarenal or extrarenal pathways. The effects of intravenous (i.v.) and renal arterial infusion of isoproterenol on PRA and renin secretion rate (RSR) were compared in anesthetized dogs. In 12 studies in 9 dogs i.v. infusion of isoproterenol (0.009-0.018 ug/kg per min) was associated with an increase in PRA from 14.7 to 35.7 ng/ml per 3 hr (P < 0.001). PRA decreased to 19.4 ng/ml per 3 hr (P < 0.001) after cessation of the infusion. In innervated kidneys RSR increased from 1640 to 5062 U/min (P < 0.02) and decreased to 2132 U/min after cessation of the infusion (P < 0.05). In denervated kidneys the control RSR was significantly lower (455 U/min) but still increased during i.v. infusion of isoproterenol to 2762 U/min (P < 0.001) and decreased to 935 U/min (P < 0.001) after the infusion was stopped. These changes in PRA and RSR were associated with an increase in cardiac output averaging 49% and a large decrease in total peripheral resistance. These effects of i.v. isoproterenol to increase RSR were not mediated by changes in renal perfusion pressure These results do not provide evidence for a role of intrarenal beta adrenergic receptors in the control of renin release and indicate that the effect of beta adrenergic stimulation with isoproterenol to increase the release of renin is mediated by an extrarenal mechanism. Since the effect of i.v. isoproterenol occurred in the absence of changes in plasma potassium concentration, renal perfusion pressure, glomerular filtration rate, renal plasma flow, and electrolyte excretion and was not abolished by renal denervation, the possibility must be considered that the effect on renin secretion is mediated by circulatory factors. The changes in systemic hemodynamics which occurred with i.v. but not renal arterial infusion of isoproterenol may be involved in the initiation of such a pathway.

Section: Methodssupporting

confidence: 80%

“…A similar extrarenal hemodynamic pathway has been proposed for the antidiuretic effect of beta adrenergic stimulation, since antidiuresis (and systemic hemodynamic changes) also occurs with i.v. but not renal arterial infusion of isoproterenol (30). Vasopressin appears to be the mediator of this antidiuretic effect of i.v.…”

Section: Methodsmentioning

confidence: 83%

An effect of extrarenal beta adrenergic stimulation on the release of renin

Reid¹,

Schrier²,

Earley³

1972

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“…In this regard, the antidiuretic effect of beta-adrenergic stimulation with isoproterenol (17) may more closely approximate the situation of impaired water excretion as observed during congestive heart failure and hemorrhage. This effect of beta-adrenergic stimulation with isoproterenol is associated with considerable systemic hemodynamic alterations and is primarily mediated by an increased release of vasopressin (17).…”

Section: Methodsmentioning

confidence: 99%

Mechanism of Suppression of Vasopressin during Alpha-Adrenergic Stimulation with Norepinephrine

Berl¹,

Cadnapaphornchai²,

Harbottle³

et al. 1974

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A B S T R A C T Recent studies have demonstrated that the water diuresis associated with intravenous infusion of norepinephrine is mediated primarly by suppression of antidiuretic hormone (ADH) release. To investigate whether the increase in cerebral perfusion pressure with intravenous norepinephrine (0.5 jg/kg/min) is directly responsible for suppression of ADH release, the carotid circulation of dogs was pump-perfused bilaterally to selectively increase cerebral perfusion pressure. In six experiments cerebral perfusion pressure was increased from a mean of 125 to 151 mm Hg and then returned to 120 mm Hg. This maneuver was not associated with a reversible increase in renal water excretion. The possibility was also examined that norepinephrine exerts a direct central effect to suppress ADH release. In 12 experiments norepinephrine was infused into the carotid artery in a subpressor dose (0.12 ,tg/kg/min) estimated to equal the amount of the catecholamine reaching the cerebral circulation with intravenous norepinephrine. The urinary osmolality (Uosm) was not significantly altered with intracarotid norepinephrine (932 to 959 mosmol/kg H20. The possibility was also examined that changes in autonomic neural tone from arterial baroreceptors is responsible for suppression of ADH release with intravenous norepinephrine. In sham-operated animals intravenous norepinephrine diminished Uosm from 1,034 to 205 mosmol/kg H20 (P < 0.001) whereas in animals with denervated arterial baroreceptors intravenous norepinephrine was not associated with a significant alteration in Uosm (1,233 to 1,232 mosmol/kg) H20. These different effects on urinary osmolality occurred in the absence of differences in plasma osmolality and volume status. The results therefore indicate that norepinephrine primarily suppresses ADH release by altering autonomic baroreceptor tone rather than by a diReceived for publication 9 July 1973 and in revised form 29 August 1973. rect central or pressor effect of the catecholamine. This same mechanism may be the primary pathway for other nonosmotic influences on ADH release. INTRODUCTIONThe effect of intravenous norepinephrine to increase renal water excretion has been well documented in both humans (1-3) and animals (4, 5). Recent experimental evidence has demonstrated that this effect of norepinephrine is primarily related to its alpha adrenergic-stimulating properties (4,5). Moreover, studies from our laboratory have shown that this effect of norepinephrine on -renal water excretion is mediated primarily by suppression of vasopressin release rather than a direct effect

“…Support that an increased level of ADH may indeed be responsible, at least in part, for the effect of sodium balance on water excretion in adrenal insufficiency is provided by the recent results of Share and Travis (21). In this regard, the recent findings of Schrier, Lieberman, and Ufferman (22) raise the possibility that changes in autonomic neural tone may be the primary pathway whereby alterations in sodium balance and body fluid volume influence ADH release. Somewhat against the possibility for a role of ADH in the present study, however, was the finding that the urine achieved a significant degree of hypotonicity, even in the studies in which an impairment in water excretion was demonstrable (group V).…”

Section: V0mentioning

confidence: 96%

Importance of sodium intake and mineralocorticoid hormone in the impaired water excretion in adrenal insufficiency

Ufferman¹,

Schrier²

1972

100

A B S T R A C T The response of trained, conscious dogs to an acute water load was studied before adrenalectomy and under five conditions of hormonal replacement and sodium intake after adrenalectomy. Before adrenalectomy, with the dogs drinking isotonic saline, the minimal urinary osmolality (Uosm) was 47±7 (SEM) mOsm and free-water clearance (CH2o) was 8.6±1 ml/min. These values were not different after adrenalectomy with or without deoxycorticosterone (DOCA) if the animals continued to drink saline and receive dexamethasone. Moreover, after adrenalectomy in the presence of saline drinking both dexamethasone and DOCA could be withdrawn for up to 4 days without impairment of diluting ability (Uosm, 544+7 mOsm and CH20, 7.3±1 ml/min).In contrast, when the dogs drank tap water (Na intake 30 mEq/day), water loading in the absence of dexamethasone and DOCA was associated with a significantly higher Uosm (127±28,mOsm) and lower CH20 (2.7+0.3 ml/min). Replacing DOCA alone in the presence of this limited Na intake returned diluting ability to normal (Uosm 31±7 mOsm, CH2o 7.7±0.5 ml/min). Glomerular filtration rate for each animal was the same under each condition except for a significant diminution which occurred when dexamethasone and DOCA were withdrawn while the animals were on a 30 mEq sodium intake. In contrast to previous conclusions, the present results indicate that in the absence of adrenal hormones normal renal diluting ability may occur, indicating both maximal suppression of vasopressin release and maximal distal tubular impermeability to water.