ROLES OF NITRIC-OXIDE AND ENDOTHELIUM-DERIVED HYPERPOLARIZING FACTOR IN VASORELAXANT EFFECT OF ACETYLCHOLINE AS INFLUENCED BY AGING AND HYPERTENSION

We investigated vasodilator responses to acetylcholine (ACh) in isolat ed mesenteric vascular bed preparations (preconstricted with methoxami ne) of young (2 months) and old (18 months) normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). ACh produced a s imilar dose-dependent vasorelaxant effect in preparations from both 2- month old normotensive and hypertensive rats. This vasodilator respons e to ACh decreased with age, especially in hypertensive animals. In pr eparations from young WKY, the vasorelaxant effect of ACh was not affe cted by 100 mu M N-G-nitro-L-arginine methyl ester (L-NAME), and was o nly slightly reduced by 500 mu M L-NAME. The K+ channel blocker tetrae thylammonium (TEA 2.5-10 mM) concentration-dependently antagonized the ACh-induced vasodilation in the same preparations. In preparations ob tained from aged WKY animals, as well as in those from young and aged SHR animals, ACh-induced vasodilation was significantly and concentrat ion-dependently reduced by 100 and 500 mu M L-NAME. On the other hand, TEA induced a lesser antagonistic effect than that observed in young normotensive animals. In preparations preconstricted with 80 mM KCl, A Ch caused vasodilation that was weaker in preparations from young WKY than in those from aged WKY; on the contrary, ACh was more effective i n young than in aged SHR. These results confirm that the vasodilating response to ACh decreases with age and hypertension and suggest that t he main mechanism responsible for the effect of ACh in vessels of youn g normotensive animals consists of activation of K+ channels. In prepa rations from old normotensive, as well as in those from young and old hypertensive animals, ACh induces vasorelaxation mainly through nitric oxide (NO) release.