ENDOGENOUS VASOACTIVE SYSTEMS AND THE PRESSER EFFECT OF ACUTE N-OMEGA-NITRO-L-ARGININE METHYL-ESTER ADMINISTRATION

The contribution of the renin-angiotensin system (RAS) and various end ogenous vasoconstrictors on the presser response to acute N-omega-nitr o-L-arginine methyl ester (L-NAME) administration (200 mu g/kg/min) wa s assessed in anesthetized Wistar rats. Activity of the endogenous RAS was suppressed either by chronic treatment by a nonpeptide angiotensi n II (AII) receptor antagonist (losartan) or an angiotensin-converting enzyme inhibitor (ACEI: enalapril), DOCA-salt pretreatment (without p revious uninephrectomy), and binephrectomy (36-40 hours before experim ents). We also studied the influence of chronic dietary sodium restric tion. The role of alpha(1)-adrenoceptor activity, endothelin (ET), and eicosanoids was evaluated in rats pretreated by prazosin, phosphorami don (a nonspecific blocker of the conversion of big ET to ET), indomet hacin, and the tromboxane A(2) (TXA(2)) prostaglandin H-2 (PGH(2))-rec eptor antagonist SQ 29548, respectively. Finally, we tested the influe nce of the calcium channel blocker nicardipine on the vasopressor effe ct of L-NAME. In nonpretreated animals, L-NAME infusion induced an inc rease in mean arterial pressure (MAP) of 38 +/- 4 mm Hg. Chronic suppr ession of the RAS by losartan, enalapril, or DOCA did not alter the re sponse to L-NAME, but the effect of L-NAME was moderately blunted in b inephrectomized rats. Moderate attenuation (similar to 25%) and to a s imilar extent of the presser effect of L-NAME was afforded by the low- sodium diet, phosphoramidon, SQ 29548, and indomethacin, whereas nicar dipine markedly blunted by 74% the effect of L-NAME. We conclude that the acute presser effect of L-NAME is mediated (at least in part) by c yclooxyenase-dependent products (mainly TXA(2)) and ET, but not by the RAS. Unmasking by L-NAME of the vasoconstrictor effect of endogenous vasoconstrictors of endothelial origin (TXA(2), ET) may be an importan t contributor to the acute presser effect of nitric oxide (NO) synthes is inhibition.