Nitric oxide participates in calcium-mediated regulation of renin release.
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)
Beierwaltes
W H
WH
Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, MI 48202-2689.
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
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