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 fjimol/L) or L-NAME (100 |xmol/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-NAMEtreated 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. We conclude that inhibition of nitric oxide synthase produces hypertension associated with mild but persistent (post-L-NAME) structural changes in resistance arteries that resemble those found in other forms of experimental hypertension, suggesting that deficient nitric oxide production does not play an important role in vascular remodeling in hypertension. The mechanism for enhanced adrenergic responses of resistance arteries after nitric oxide synthase inhibition occurs at the level of adrenergic receptors or at a postreceptor level. Because this effect is still present in the post-L-NAME stage, albeit to a lesser degree, there may be a structural component to this phenomenon. Am J Hypertens 1994;7:996-1004
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Li et al. (1994) studied this question.