Vascular smooth muscle contraction is an independent regulator of endothelial nitric oxide production

This investigation was conducted to determine whether endothelial nitric ox ide (NO) production is regulated by vascular smooth muscle contraction. Unp erfused ring segments of rat aorta and mesenteric artery were studied using isometric tension recording (n = 6-8 in all experiments). Following a refe rence contraction to K+ 80 mM (100%), arteries were left either unstimulate d or stimulated by different concentrations of K+ or prostaglandin F-2 alph a (PGF(2 alpha)) to induce different levels of vascular precontraction. N-G -nitro-L-arginine methyl ester (L-NAME 0.1-300 mu M) or NS 2028 (0.03-3 mu M), which is a new specific inhibitor of the NO-sensitive guanylate cyclase , was then added at increasing concentrations to evaluate endothelial NO pr oduction. L-NAME and NS 2028 produced a concentration-dependent vasoconstri ctor response which was progressively enhanced with increasing levels of pr econtraction. For L-NAME, this amounted in aorta to (% of reference contrac tion): 35 +/- 1% and 105 +/- 4% (precontraction by K(+)20 and 30 mM) and 22 +/- 1%, 89 +/- 1%, 138 +/- 1% and 146 +/- 2% (precontraction by PGF(2 alph a) 0.5, 1, 2 and 3 mu M). A similar coupling was found in the mesenteric ar tery. A precontraction as little as 2% was enough to trigger a vasoconstric tor response to L-NAME. In contrast, L-NAME and NS 2028 had no effect in no n-contracted arteries, not even when passive mechanical stretch was increas ed by 100%. The results suggest (i) that endothelial NO formation is progre ssively increased with increasing vascular tone, and (ii) that vascular iso metric contraction per se stimulates endothelial NO formation. It is conclu ded, that active vascular smooth muscle contraction is an independent regul ator of endothelial NO production.