Using a recognized inhibitor of nitric oxide (NO) synthesis, Nw-nitro L-arginine methyl ester (L-NAME), we tested the hypothesis of the existence of a nonendothelial source of NO in vascular tissue using rings of rat thoracic aorta in which endothelial cells have been removed by mechanical abrasion and have totally lost their endothelium-dependent relaxation. Contractility of the muscle was tested by recording the concentration-dependent contraction of the preparations induced by an α-adrenergic agonist, phenylephrine. Contractility in aortas from Wistar-Kyoto normotensive rats (WKY) and spontaneous hypertensive rats (SHR) was not significantly affected by a 30-min to 2-hour incubation with L-NAME prior to agonist stimulation. However, preparations incubated for 30 min with 1 mM L-arginine (L-ARG) and then washed for 1 h in standard Krebs solution had a significantly reduced contraction to phenylephrine in both WKY and SHR. In these preparations pretreated with L-ARG, L-NAME significantly increased contractility in both WKY and SHR; this effect was prevented by L-ARG but not by D-arginine. Responses to phenylephrine were not inhibited by L-ARG when preparations were incubated from the beginning of the experiment with 1 mM cycloheximide, thus suggesting a dependence on protein synthesis of the attenuation of contraction seen with L-ARG. Intact aortic rings processed for NADPH diaphorase histochemistry, a putative marker for NO synthase, showed NADPH diaphorase reactivity only in the endothelial layer and in the adventitia. We concluded that there is a nonendothelial source of NO in rat aorta but that the enzymatic reaction responsible for NO production was inactive under the usual in vitro conditions due to a lack of substrate, L-ARG. The lack of differences between the two strains of rats seems to rule out the possibility of a difference in the mechanism or the existence of a nonendothelial source of NO which could be linked to the pathophysiology of blood vessels in hypertension.

Keywords:
Nitric oxide synthase, NADPH diaphorase, Hypertension, L-Arginine, Nw-Nitro L-arginine methyl ester
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© 1992 S. Karger AG, Basel
1993
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