Nitric oxide synthesis influences the renal vascular response to heme oxygenase inhibition.

We studied the effects of the heme oxygenase (HO) inhibitor stannous mesoporphyrin (SnMP; 40 micromol/kg i.v.) on renal hemodynamics in anesthetized rats with and without 48-h pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis. SnMP decreased renal blood flow (RBF) and increased renal vascular resistance (RVR) in both groups. The SnMP-induced reduction of RBF in L-NAME-pretreated rats was more prominent than in rats without pretreatment (43 +/- 7 vs. 13 +/- 3%) as was the SnMP-induced elevation of RVR (87 +/- 31 vs. 14 +/- 5%). The renal vasoconstrictor effect of SnMP is linked, in part, to amplification of prevailing neurohormonal constrictor mechanisms, since in L-NAME-pretreated rats it was prevented by concurrent administration of prazosin or losartan. However, SnMP (15 micromol/l) also elicits vasoconstriction in isolated, pressurized renal interlobular arteries and the response is more intense in vessels obtained from L-NAME-pretreated rats than from rats without pretreatment. These data indicate that the status of NO synthesis conditions the vascular response to HO inhibition in the rat kidney.