Prorenin secretion from villous placenta: regulation by cyclic AMP and angiotensin

Renin synthesis and secretion from human chorion and decidua have previously been shown to be stimulated by agents which increase cellular cyclic adenosine monophosphate (cAMP). We have now used organ culture of villous placenta, incubated for periods up to 72 h, to investigate the cellular regulation of renin in this tissue. The placental tissues release renin (92-96% in the form of prorenin) and human chorionic gonadotrophin (hCG), but not prolactin. We found that cholera toxin and forskolin markedly stimulate the synthesis and release of renin in a time-dependent manner. This stimulation was potentiated by phosphodiesterase inhibitors and inhibited by an angiotensin II agonist, sar-1-angiotensin II. The inhibitory action of the angiotensin agonist on renin release was blocked by sar-1-leu-8-angiotensin II, a selective angiotensin receptor antagonist. The potential for stimulation of renin expression by cyclic AMP-regulated elements is supported by the dramatic (two-orders of magnitude) increase in renin release observed with cholera and forskolin at 72 h. There are several possible candidates for primary signals for adenylyl cyclase-coupled renin secretion from the placenta, including relaxin and epinephrine. The extremely low concentration of renin in term villous placenta may be related to activation of negative regulatory elements on the renin gene. We propose that angiotensin II is one negative regulator of this system.