Integrative effects of nitric oxide and endothelium-derived hyperpolarizing factor induced by acetylcholine and...

We investigated the roles of endothelium-derived vasodilative factors in rat hindquarter perfusion using a system for the direct measurement of nitric oxide (NO). Acetylcholine (ACh) induced the dose-dependent release of NO with a concomitant decrease in perfusion pressure. Under the influence of N(G)-monomethyl-l-arginine (l-NMMA), NO release in response to ACh was blocked, while the perfusion pressure still decreased. In the presence of tetraethylammonium (TEA), the decrease in perfusion pressure in response to ACh was attenuated compared to the control value. The decrease in perfusion pressure in response to ACh was almost abolished in the presence of both l-NMMA and TEA or with deendothelialization. Bradykinin (BK) also induced NO release and biphasic effects on the perfusion pressure. The perfusion pressure decreased with a lower concentration of BK and increased with a higher concentration. l-NMMA and TEA each abolished the decrease in perfusion pressure induced by BK. Furthermore, in the presence of both l-NMMA and TEA, the perfusion pressure actually increased in response to BK. These results suggest that ACh and BK induce vasodilation through NO release and a potassium channel dependent mechanism via endothelium.