Hydralazine prevents endothelial dysfunction, but not the increase in superoxide production in nitric oxide-deficient hypertension.
Dilator responses, superoxide anion-production, endothelial nitric oxide (NO) synthase and soluble guanylyl cyclase expression were determined in aortic rings from Wistar rats treated for 5 weeks either with the NO synthase inhibitor NG-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/hydralazine group. This difference was even more pronounced following inhibition of the endogenous superoxide dismutase using diethyldithiocarbamate. Aortic superoxide production was significantly elevated in both L-NAME-treated groups and hydralazine had no acute effect on superoxide formation. Expression 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 improves vasodilator responses but not the increased superoxide production.
Bauersachs
J
J
II. Medizinische Klinik, Universitätsklinikum Mannheim, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Germany. johann.bauersachs@med2.ma.uni-heidelberg.de
Bouloumié
A
A
Fraccarollo
D
D
Hu
K
K
Busse
R
R
Ertl
G
G
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D004050:Ditiocarb / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism; D006830:Hydralazine / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D066298:In Vitro Techniques; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D006830:Hydralazine; D009569:Nitric Oxide; D004050:Ditiocarb; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D006162:Guanylate Cyclase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester