Resistance artery structure and neuroeffector mechanisms in hypertension induced by inhibition of nitric oxide synthase.
Oral administration of NW-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, results in blood pressure elevation. In this study we investigated resistance artery structure and neuroeffector mechanisms in rats treated with L-NAME. After 5 days of treatment the morphology of resistance arteries was unchanged, whereas after 2 or 4 weeks, when rats were hypertensive, the media was thicker and the media-to-lumen ratio was enhanced. When L-NAME administration was stopped for 2 weeks, the media-to-lumen ratio remained increased. At all time periods under L-NAME and 2 weeks after stopping treatment, the dose-response to norepinephrine was significantly more sensitive than in controls, with a concomitant slight increase in efficacy. Cocaine (3 mumol/L) or L-NAME (100 mumol/L) applied in vitro produced a leftward displacement of the dose-response of arteries from controls to norepinephrine, and abolished the difference with vessels from L-NAME-treated rats. Responses evoked by electrical field stimulation were also displaced to the left in L-NAME-treated rats and by L-NAME in vitro, and exhibited a slight increase in maximal response. Dose-response curves to methoxamine, which is not subject to neuronal reuptake, were displaced to the left by L-NAME in vivo and in vitro, similarly to those of norepinephrine, but were not displaced by cocaine in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Li
J S
JS
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
Schiffrin
E L
EL
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced*; D008729:Methoxamine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009451:Neuroeffector Junction / Q000187:drug effects*; D019001:Nitric Oxide Synthase; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D008729:Methoxamine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine