Control of the renal renin system by local factors.

Local factors, such as prostaglandins (PGs), nitric oxide (NO), and endothelins (ETs), produced in the immediate vicinity of juxtaglomerular (JG) cells can exert significant effects on renin secretion and renin gene expression. PGE2, as the main renotubular PG, and PGI2, as the main endothelial prostanoid, both stimulate renin secretion and renin gene expression by activating cAMP formation in JG cells. Although the direct effect of NO on JG cells is less clear, its overall effect in vivo seems to be to stimulate the renin system. Evidence is emerging that stimulation by NO is related to the cAMP pathway, and cGMP-induced inhibition of cAMP-phosphodiesterase III (PDE-III) may mediate this effect. ETs, on the other hand, appear to inhibit the renin system, in particular in those pathways activated by cAMP, acting via Ca2+- and protein kinase C-related mechanisms. There is increasing evidence that both NO and PGs could be involved in the physiological regulatory mechanisms by which salt intake affects the renin system.