Ca 2+-dependent modulation of renin release from isolated glomeruli: Apparent independence from alterations in cGMP

Abstract

This study examined the role of cGMP in the control of renin release from isolated rat glomeruli. An inverse correlation between renin release and cGMP content of isolated glomeruli was found under several conditions of incubation. Thus, incubation of isolated glomeruli in Ca 2+-free media containing EGTA, or the addition of the Ca 2+ and calmodulin (CaM) antagonists trifluoperazine (TFP), N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide hydrochloride (W-7), or (8-N, N-diethylamino)-octyl 3,4,5-trimethoxybenzoate-HCl (TMB-8) to glomeruli incubated in Ca 2+ replete buffer lowers cGMP and stimulates renin release. These same incubation conditions enhance the release of renin induced by isoproterenol (DBcAMP) in isolated glomeruli. By contrast, raising media K + to 60 mmol/L, or the incubation of glomeruli with angiotensin II (A-II) or ouabain—all of which are thought to increase intracellular Ca 2+—increased glomerular cGMP and suppressed basal glomerular renin release and the increases in renin release induced by isoproterenol (DBcAMP). However, neither exogenous DBcAMP nor nitroprusside, and agent that increased the endogenous cGMP, content of glomeruli mimicked the suppressive effects of high K +, A-II, or ouabain on renin release. Moreover, DBcGMP and nitroprusside also failed to reverse the stimulatory effects of Ca 2+ deprivation, TFP, W-7, or TMB-8 on glomerular renin release, even though nitroprusside clearly enhanced cGMP under these conditions of incubation. The results suggest that changes in glomerular cGMP and renin release occur concomitantly in response to alterations in glomerular Ca 2+ homeostasis, but that cGMP does not mediate the changes in glomerular renin release.