Hydralazine prevents endothelial dysfunction, but not the increase in superoxide production in nitric oxide-deficient hypertension

Dilator responses, superoxide anion-production, endothelial nitric oxide (N O) synthase and soluble guanylyl cyclase expression were determined in aort ic rings from Wistar rats treated for 5 weeks either with the NO synthase i nhibitor N-G-nitro-L-arginine-methylester (L-NAME), L-NAME plus hydralazine or placebo. In the L-NAME-treated group, acetylcholine-induced relaxation was significantly attenuated whereas it was nearly normal in the L-NAME/hyd ralazine group. This difference was even more pronounced following inhibiti on of the endogenous superoxide dismutase using diethyldithiocarbamate. Aor tic superoxide production was significantly elevated in both L-NAME-treated groups and hydralazine had no acute effect on superoxide formation. Expres sion of endothelial NO synthase was similar in all three groups whereas the attenuated soluble guanylyl cyclase expression in rats treated with L-NAME was nearly normalised by concomitant hydralazine treatment. These results demonstrate that in NO-deficient hypertension hydralazine treatment improve s vasodilator responses but not the increased superoxide production. (C) 19 98 Elsevier Science B.V. All rights reserved.