Ca2+-dependent modulation of renin release from isolated glomeruli: apparent independence from alterations in cGMP.
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 Ca2+-free media containing EGTA, or the addition of the Ca2+ 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-HCI (TMB-8) to glomeruli incubated in Ca2+ 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 Ca2+--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, an 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 Ca2+ 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 Ca2+ homeostasis, but that cGMP does not mediate the changes in glomerular renin release.
P A
PA
Craven
F R
FR
DeRubertis
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*
D002147:Calmodulin; D000804:Angiotensin II; D009599:Nitroprusside; D010042:Ouabain; D011189:Potassium Chloride; D012083:Renin; D006152:Cyclic GMP; D007545:Isoproterenol; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine