Potassium‐angiotensin interplay in the regulation of aldosterone biosynthesis

Abstract

Although the biosynthesis of aldosterone in the zona glomerulosa of the adrenal cortex is known to be regulated by a whole array of other agents (ACTH, serotonin, dopamine, atrial natriuretic peptide, acetylcholine) (Miiller, 1988) in this short review we will concentrate on the interplay between the two major regulators, angiotensin I1 and potassium ion ( K ' ) . For many years, specific diseases as well as pathophysiological clinical situations have taught us much about the relation between the renin-angiotensin system and potassium, which has been further explored by animal experimentation. More recently, considerable progress has been achieved in our understanding of the mode of action of both angiotensin I1 and K+ at the cellular level, putting their interplay into a new light. Clinical obsewatlonsThere are many diseases and clinical settings which are caused by abnormalities of secretion of one or other member of the renin-angiotensin system and of the mineralocorticoid family of compounds, mainly aldosterone, or in which these hormones react to or adapt to disturbances of potassium economy. The latter is easily disturbed, which is not surprising given that the total potassium available in the extracellular fluid is 65 mmol, compared with some 5 mol of intracellular potassium. This is distributed mainly in muscle (approximately 2650 mmol), with the erythrocytes, liver and bones each accounting for approximately 250-300 mmol. The turnover of body potassium reflects a daily intake of approximately 100 mmol in the diet, and equivalent excretion mainly by the kidney and to a smaller extent in the stool.In circumstances under which the renin-angiotensin system is primarily stimulated, secondary hyperaldosteronCorrespondence: Professor M.

TASK channel deletion in mice causes primary hyperaldosteronism

“…Ang II and extracellular K are potent independent regulators of aldosterone production, yet the strength of these agonists in the physiological setting depends on their combined activities and their synergy (11)(12)(13)(14). Small elevations in plasma potassium within the physiological range increase the sensitivity of ZG cells to stimulation by Ang II (13,15). In this setting, both K and Ang II mediate membrane depolarization of ZG cells (14,16) to enhance the opening of Ang II-modulated, low-voltage-activated, Ca channels (Cav3.2) whose activity underlies the in vivo control of aldosterone production (17,18).…”

Confinement of intracellular calcium signaling in secretory and steroidogenic cells

“…Whereas the capacitative influx is activated only as a consequence of Ca 2+ release from the store by Ins(1,4,5)P 3 , Ca 2+ entering through T-type channels overloads Ca 2+ into the pipeline, causing its release near mitochondria, even at basal concentrations of Ins(1,4,5)P 3 . Thus, this model could partly explain the potentiating actions of low [K + ] and AngII on aldosterone secretion if one considers that Ca 2+ entering through T-type channels helps the capacitative pathway to refill the store upon mobilization of Ca 2+ by Ins(1,4,5)P 3 (80). Another difference, at least in bovine cells, is the coupling of the capacitative influx, but not of T-type channels, with cAMP production (Fig.…”

Ectopic expression of serotonin7 receptors in an adrenocortical carcinoma co-secreting renin and cortisol

“…However, we could not verify this potential mechanism since plasma renin activity was not measured. It is also possible that the lack of elevation of plasma aldosterone concentration was the consequence of hypokalemia which is known to lower in vivo the stimulatory effect of Ang II on aldosterone secretion by the zona glomerulosa (Vallotton et al 1995). During the postoperative period, the moderate decrease in aldosterone levels (K27%) observed postoperatively did not parallel the important decline in renin concentrations (K88%).…”