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 prostaglandins and nitric oxide (NO) in the renin stimulatory effect of angiotensin II (AngII) antagonists. To this end, plasma renin activities (PRAs) and renal renin mRNA levels were assayed in rats that were treated with the Ang-converting enzyme inhibitor ramipril or with the AngII AT1-receptor antagonist losartan. Ramipril and losartan increased PRA values from 7.5 +/- 1.6 to 86 +/- 6 and 78 +/- 22 ng of AngI per h per ml and renin mRNA levels from 112 +/- 9% to 391 +/- 20% and 317 +/- 10%, respectively. Inhibition of prostaglandin formation with indomethacin did not influence basal or ramipril-affected PRA. Basal renin mRNA levels also were unchanged by indomethacin, while increases in renin mRNA levels after ramipril treatment were slightly reduced by indomethacin. 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 ml in control, ramipril-treated, and losartan-treated animals, respectively. Renin mRNA levels were reduced to 77 +/- 14% 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 counteracted by AngII.
Schricker
K
K
Physiologisches Institut der Universität Regensburg, Germany.
Hegyi
I
I
Hamann
M
M
Kaissling
B
B
Kurtz
A
A
D000704:Analysis of Variance; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004792:Enzyme Precursors / Q000096:biosynthesis*; D004794:Enzyme Repression; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000096:biosynthesis* / Q000097:blood; D013777:Tetrazoles / Q000494:pharmacology
D001713:Biphenyl Compounds; D004792:Enzyme Precursors; D007093:Imidazoles; D012333:RNA, Messenger; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D001120:Arginine; D012083:Renin; D019808:Losartan; D017257:Ramipril; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin