ENDOTHELIUM-DERIVED RELAXING FACTOR RELEASED BY 5-HT - DISTINCT FROM NITRIC-OXIDE IN BASILAR ARTERIES OF NORMOTENSIVE AND HYPERTENSIVE RATS

1 The role of the endothelium in cerebrovascular responses to 5-hydroxytryptamine (5-HT) was investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) in vitro. 2 Cumulative addition of 5-HT caused concentration-dependent contractions in ring preparations of SHR basilar arteries; the contractile response was smaller in WKY basilar arteries. 3 Removal of the endothelium enhanced markedly the contractile responses to 5-HT in WKY arteries but had only a slight effect in SHR arteries. The responsiveness to 5-HT in WKY arteries after removal of endothelium was comparable to that in SHR arteries. 4 The endothelium-dependent relaxation induced by acetylcholine in WKY basilar arteries was almost abolished by treatment with 10 mu M methylene blue or 10 mu M N-G-nitro-L-arginine (L-NOARG). However, the response to 5-HT was not affected by treatment with methylene blue, L-NOARG or indomethacin. 5 Application of 10-20 mM K+ or 3.2 mM tetraethylammonium (TEA) did not change significantly, or only increased slightly, the resting tension, but markedly enhanced the contractile response to 5-HT in WKY arteries with endothelium. In contrast, the submaximal response to 5-HT in SHR arteries with endothelium was significantly enhanced by 0.3 mM TEA. 6 In the presence of 1 mM TEA, the application of 10 mu M L-NOARG further enhanced the responses of 5-HT in WKY arteries with endothelium. In SHR arteries with endothelium, 10 mu M L-NOARG per se enhanced slightly but significantly the responses to 5-HT. 7 These results indicate that 5-HT-induced contraction in basilar arteries is substantially attenuated by an endothelium-dependent mechanism in WKY, but to a much lesser extent in SHR. The major relaxing factor released by 5-HT from endothelium in WKY is distinct from NO and may exert its effect by activating K+ channels.