title: Nitric oxide participates in calcium-mediated regulation of renin release.
abstract: The regulation of renin release is unusual in that intracellular calcium reportedly acts as an inhibitory second messenger. Increased calcium not only inhibits renin release but is a cofactor in nitric oxide synthesis. Also, nitric oxide can inhibit renin release. This study was done in vitro using rat renal cortical slices to determine whether calcium-mediated renin inhibition could be in part due to the concurrent production of nitric oxide. Renin concentration in the incubation medium was determined by radioimmunoassay for angiotensin I (Ang I) generation (in nanograms Ang I per hour per milligram per 30 minutes of incubation). In all studies, n = 6 to 17. In normal-calcium incubation medium (2.6 mmol/L), 10(-4) mol/L NG-monomethyl L-arginine, which blocks nitric oxide synthesis, caused an 18% increase in basal renin release (78.6 +/- 8.9 versus 66.7 +/- 5.8 [ng Ang I/h]/mg per 30 minutes incubation, P < .05). When calcium was eliminated from the incubation medium, basal renin release doubled (to 133.1 +/- 15.2 [ng Ang I/h]/mg per 30 minutes incubation, P < .001). Without calcium, inhibiting nitric oxide synthesis had no further effect on renin release (126.8 +/- 17.7 [ng Ang I/h]/mg per 30 minutes incubation). High-calcium medium (7.8 mmol/L) reduced basal renin release by half (30.8 +/- 4.8 [ng Ang I/h]/mg per 30 minutes incubation, P < .001), but inhibiting nitric oxide synthesis in high-calcium medium stimulated renin release by 50% (46.9 +/- 6.2 [ng Ang I/h]/mg per 30 minutes incubation, P < .005). Addition of the calmodulin inhibitor W-7 completely reversed the inhibition of renin by high-calcium medium.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, MI 48202-2689.
authors.forename: W H
authors.initials: WH
authors.lastname: Beierwaltes
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D019323:omega-N-Methylarginine
chemical_list: D002147:Calmodulin; D013449:Sulfonamides; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004533:Egtazic Acid; C017967:W 7; D001120:Arginine; D012083:Renin; D007545:Isoproterenol; D002118:Calcium