TONIC STIMULATION OF RENIN GENE-EXPRESSION BY NITRIC-OXIDE IS COUNTERACTED BY TONIC INHIBITION THROUGH ANGIOTENSIN-II

This study was designed to examine the possible involvement of prostag landins and nitric oxide (NO) in the renin stimulatory effect of angio tensin II (AngII) antagonists, To this end, plasma renin activities (P RAs) and renal renin mRNA levels were assayed in rats that were treate d with the Ang-converting enzyme inhibitor ramipril or with the AngII. AT(1)-receptor antagonist losartan. Ramipril and losartan increased P RA values from 7.5 +/- 1.6 to 86 +/- 6 and 78 +/- 22 ng of AngI per h per mi and renin mRNA levels from 112 +/- 9% to 391 +/- 20% and 317 +/ - 10%, respectively, Inhibition of prostaglandin formation with indome thacin did not influence basal or ramipril-affected PRA. Basal renin m RNA levels also were unchanged by indomethacin, while increases in ren in mRNA levels after ramipril treatment were slightly reduced by indom ethacin, Inhibition of NO synthase by nitro-L-arginine methyl ester (L -NAME) reduced PRA values to 3.2 +/- 0.9, 34 +/- 13, and 12.1 +/- 2.7 ng of AngI per h per mi in control, ramipril-treated, and losartan-tre ated animals, respectively, Renin mRNA levels were reduced to 77 +/- 1 4% under basal conditions and ramipril- and losartan-induced increases in renin mRNA levels were completely blunted after addition of L-NAME , The AngII antagonists, furthermore, induced an upstream recruitment of renin-expressing cells in the renal afferent arterioles, which was also blunted by L-NAME. These findings suggest that renin mRNA levels are tonically increased by NO and that the action of NO is counteracte d by AngII.