Role of calcium in angiotensin II-mediated aldosterone secretion

The synthesis and secretion of aldosterone by adrenal glomerulosa cells is under the control of three major stimulatory extracellular messengers: angiotensin II (Ang II), extracellular potassium (K⁺), and ACTH (1, 2). Although in certain species PTH (3), vasopressin (4, 5), and acetylcholine (6) also enhance the aldosterone secretory response, the universal physiological role of these agonists in vivo is not yet clear. In addition to stimulatory extracellular messengers, several hormones exert inhibitory effects. The most prominent of these is atrial natriuretic peptide (ANP), but in some species both dopamine and somatostatin also cause inhibition (7–9). The present discussion will focus on the role of calcium (Ca²⁺) in the acute (hours vs. days) regulation of aldosterone secretion by Ang II. Two traditional signaling pathways have been identified in the glomerulosa cell. The first is the stimulation of adenylate cyclase activity with the consequent production of cAMP and the activation of cAMP-dependent protein kinases. ACTH and PTH activate this pathway. The second is the stimulation of phosphoinositide-specific phospholipase C (PLC) with the consequent production of inositol trisphosphate (InsP₃) and membrane diacylglycerol (DAG) and the activation of protein kinase C. This sequence of events is initiated in response to Ang II, acetylcholine, and vasopressin. In contrast, antagonists of aldosterone secretion may act either by altering the production of stimulatory second messengers, or by inducing the production of their own second messengers, which in turn negatively modulate the activated secretory pathways. ANP may employ each of these modes of action.