Role of angiotensin: insight from gene targeting studies

We and others have recently produced, by gene targeting, several strains of mice deficient of a specific gene within the renin-angiotensin system. Detailed examination of these mutant mice not only confirmed the well-known blood pressure raising action of angiotensin II, but also revealed several important biological functions of angiotensin II that have not been well recognized, most notably the role in the ontogenesis of the kidney. Since gene targeting causes complete inactivation of the targeted gene, this approach also allows us to address the question, "is angiotensin really essential for the induction of aldosterone during ECF volume depletion?" In our studies, we obtained unequivocal evidence indicating that angiotensin is not essential, but instead, potassium becomes an effective regulator for aldosterone during extracellular fluid (ECF) volume depletion through mechanisms that are indistinguishable from those of angiotensin, that is, selective stimulation of aldosterone synthetase and proliferation of zona glomerulosa cells within the adrenal gland. In this context, angiotensin can be regarded as a modifier of K-dependent aldosterone regulation.