Effect of hydrogen ion concentration on aldosterone secretion by isolated perfused canine adrenal glands

Abstract

The direct effects of changes in extracellular hydrogen ion (H+) concentration on aldosterone secretion under basal, angiotensin II- and potassium-stimulated conditions were studied in isolated, perfused canine adrenal glands. Changes in extracellular H+ concentration were induced by altering either the partial pressure of CO2 (pCO2) or the HCO3- concentration of the perfusate. Acid-base disturbances had a more pronounced effect on aldosterone secretion under stimulated than under basal conditions. Increasing H+ concentration enhanced angiotensin II- and potassium-stimulated aldosterone secretion, whereas decreasing H+ concentration markedly inhibited the secretory response to these stimuli. Because changes in H+ concentration, whether produced by varying extracellular pCO2 or extracellular HCO3- concentration, had similar effects on angiotensin II-stimulated aldosterone secretion, the data suggest that H+ concentration per se is the important determinant of the aldosterone secretory rate. Interestingly, during the immediate recovery period from pCO2-induced alkalosis under both angiotensin II- and potassium-stimulated conditions, aldosterone secretion always returned to a value significantly higher than that obtained just before alkalosis. The results of this study demonstrate that changes in extracellular H+ concentration influence the rate of aldosterone secretion, possibly via changes in intracellular pH, by a direct action on the canine adrenal gland. Therefore, when evaluating the control of aldosterone secretion, the acid-base status of the whole animal or of in-vitro adrenal tissue must be considered.

Direct modulation of basal and angiotensin II-stimulated aldosterone secretion by hydrogen ions

“…A decrease in pH i in glomerulosa cells occurs in response to extracellular acidification, and alterations of pH i have been implicated in the stimulation of aldosterone secretion by AngII and K + (Horiuchi et al 1989, Conlin et al 1990 -induced Ca 2+ release, and diacylglycerol-induced association of protein kinase C with plasma membrane in other cell types (Albuquerque & Leffler 1998, Hulme & Orchard 1998, Nishino et al 1998 Peng et al 1998, Wu & Fry 1998, Kourie 1999 (Schneider & Kramer 1986, Wang et al 1992 and [Na + ] o (Saruta et al 1972, Lobo et al 1978, that influence aldosterone secretion through Ca 2+ -dependent mechanisms. Indeed, results of the present studies confirm previous reports (Chiu & Freer 1978, Radke et al 1986b, Raff & Jankowski 1993 (Chiu & Freer 1978). In the present studies, only the secretory response to AngII was increased, albeit by a smaller reduction of pH o (from 7·4 to 7·0).…”

“…Further, an effect of H + to increase the transfer of cholesterol to mitochondria, with or without a concomitant effect to increase its translocation from the outer to the inner membrane, could account for the greater Ca 2+ sensitivity of AngII-stimulated aldosterone secretion. Jefcoate & Boyd (1971) presented evidence that H + directly stimulated cholesterol side-chain cleavage in isolated bovine adrenocortical mitochondria, and Radke et al (1986b) suggested that H + increased the conversion of corticosterone to aldosterone by perfused canine adrenals. However, neither the rate of pregnenolone production from endogenous cholesterol nor the rate of aldosterone production from exogenous corticosterone was affected by reduction of pH o from 7·2 to 6·8 (Raff & Jankowski 1993).…”

Angiotensin II receptors mediate increased distal nephron acidification caused by acid retention

“…Nevertheless, kidney epithelial cells make and secrete ET-1 31 and might also be a source of the augmented kidney ET-1. In addition, increasing perfusate acidity augments Aldo secretion from isolated perfused adrenal glands, 32 and H þ -inducing dietary protein 23,33 and NH 4 Cl 34 increase plasma Aldo in rats and humans, respectively. Additional studies will be necessary to determine precisely how H þ retention associated with reduced GFR increases kidney AII, ET-1, and Aldo levels.…”

Acid retention accompanies reduced GFR in humans and increases plasma levels of endothelin and aldosterone

“…In vitro studies show that an acid extracellular environment increases ET release from human glomerular endothelial cells (33) and that a more acid perfusate increases aldosterone release from isolated, perfused adrenal glands (23). Consequently, CKD 2 subjects appear to be able to sense an aspect of retained H ϩ .…”