A Study of the Mode of Action of the Adrenal Medullary Hormones on Sodium, Potassium and Water Excretion in Man12

199

In normal subjects, the rate of aldosterone secretion fluctuates widely according to the state of salt and water balance, but the pathways mediating this relationship are still to be identified. Hypersecretion of aldosterone occurs in malignant nephrosclerosis (2). Angiotensin, the pressor peptide released from plasma by renin, increases both the adrenal secretion (3) and the urinary excretion (4) of aldosterone in man. These observations support the suggestion (5) that a renaladrenal interaction might be involved in the normal regulation of sodium and potassium balance. By this mechanism, the kidney, perhaps sensitive to diminished arterial filling or ischemia, secretes renin, generating angiotensin, which then stimulates aldosterone secretion. Aldosterone, in turn, restores renal perfusion by promoting sodium and water retention.In malignant hypertension this mechanism may become deranged, leading to the coexistence of increased amounts of both angiotensin and aldosterone in the blood, a possibility that derives additional support from the earlier report (6) of increased blood angiotensin in these patients. On the other hand, since neither renin nor angiotensin has been conclusively demonstrated in normal human plasma, elaboration of these substances in malignant hypertension might be simply a consequence of severe renal damage.Our more recent work has investigated the possibility that this renal-adrenal interaction participates in normal homeostasis, as well as in the *This report was presented in part at the 54th an-

Section: Discussionsupporting

confidence: 92%

“…Pressor or subpressor dosages of norepinephrine, epinephrine, or angiotonin produced sodium chloride retention that could not be accounted for by changes in GFR (25,26). More recently, other groups (20)(21)(22)(23)(24)(25)(26)(27)(28) jects, angiotensin regularly produces sodium chloride retention with either no change or a fall in GFR.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin Ii, Norepinephrine, and Renal Transport of Electrolytes and Water in Normal Man and in Cirrhosis With Ascites*

Laragh

Cannon²,

Bentzel³

et al. 1963

199

“…The other naturally occurring catecholamines, epinephrine and norepinephrine, usually decrease ERPF and UNaV when administered in doses that increase arterial pressure (20). When these catecholamines are administered in doses that produce minimal effects on blood pressure, ERPF frequently falls (21,22).…”

Section: Discussionmentioning

confidence: 99%

Effects of Dopamine in Man: Augmentation of Sodium Excretion, Glomerular Filtration Rate, and Renal Plasma Flow*

McDonald¹,

Goldberg²,

McNay³

et al. 1964

486

148

Dopamine (3,4-dihydroxyphenylethylamine) is considered to be the immediate metabolic precursor of norepinephrine (1), from which it differs by the absence of a P-OH group. Despite this chemical similarity, previous studies of the action of dopamine (2-9) have demonstrated that many of the circulatory and metabolic effects of this catecholamine are different from those produced by norepinephrine. Horwitz, Fox, and Goldberg (6) observed that intravenous administration of dopamine to normal subjects produced consistent increases in cardiac output and either decreased or did not change peripheral resistance. Norepinephrine, on the other hand, decreases or does not change cardiac output and increases peripheral resistance in normal subjects (10). The circulatory effects of dopamine are potentiated by monoamine oxidase inhibitors to a much greater extent than are those of norepinephrine (9). Dopamine also contrasts with norepinephrine in its failure to increase circulating free fatty acids (7,8). These differences suggest that the effects of

“…The results of studies in humans (1)(2)(3)(4), rats (5,6), and the toad bladder (7,8) have suggested that alpha adrenergic stimulation may antagonize the action of vasopressin at the cellular level. This is an attractive hypothesis since the effect of vasopressin appears to be mediated by adenyl cyclase, an enzyme which in several tissues has been shown to be inhibited by alpha adrenergic stimulation and activated by beta adrenergic stimulation (9,10).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Antidiuretic Effect of Beta Adrenergic Stimulation

Schrier¹,

Lieberman²,

Ufferman³

et al. 1972

115

A B S T R A C T The effect of beta adrenergic stimulation on renal-diluting capacity was examined in the dog. Beta adrenergic stimulation with intravenous isoproterenol significantly increased urinary osmolality (Uo.m) and decreased free water clearance (CH:}O), and these effects were rapidly reversible with cessation of the infusion. This antidiuretic effect of systemic beta adrenergic stimulation was comparable in innervated and denervated kidneys and was not associated with alterations in glomerular filtration rate or renal vascular resistance. Renal perfusion pressure was maintained constant in all of the experiments. The same dose of isoproterenol, which produced the antidiuretic effect and markedly stimulated cardiac beta adrenergic receptors when infused intravenously, was not found either to increase Uosm or to decrease CH2O when infused directly into the renal artery. Removal of the source of production and release of antidiuretic hormone (ADH) was, however, found to abolish the effect of intravenous isoproterenol on Uoar. A small effect on CH20 persisted and appeared to be related to an increase in arterial hematocrit. Thus, the results of the study exclude a major role of alterations in renal hemodynamics and renal innervation in the antidiuretic response to betaadrenergic stimulation with isoproterenol. They also provide no support for the hypothesis that beta adrenergic stimulation may directly alter the water permeability of the renal tubular epithelium. Rather the results suggest that the primary mechanism of the antidiuretic effect of beta adrenergic stimulation involves the integrity of the hypothalamoneurohypophyial system and the release of ADH.