Critical role of endothelial nitric oxide synthase and cyclooxygenase in response of rabbit Basilar artery to serotonin

The modes of action of serotonin (5-HT) on the tone of the rabbit basilar artery were investigated in vitro with the aim of determining the exact role of the endothelium. After sacrificing the animal under pentobarbital anesthesia, 3-mm segments of the artery were removed and mounted in a 5-ml myograph for isometric tension recording. Vessels precontracted by histamine were relaxed by acetylcholine. Mean maximum relaxation at 10(-4)M was reduced from 79% to 22% (P<0.001) by 10(-5) M N-omega-nitro-L-arginine (L-NA), and from 73% to 63% (NS) by 3.10(-6) M indomethacin. Intact non-precontracted vessels were contracted by 5-HT (10(-9) M to 10(-5) M): 10(-5) M L-NA significantly increased the contractile force (approximately twofold), whereas 3.10(-6) M indomethacin significantly decreased it (to approximately 35%). In histamine-precontracted vessels, 5-HT induced at low concentrations (3.10(-9) M to 3.10(-8) M) a reduction in tone and induced an increase in tone at higher concentrations. At 10(-5) M, L-NA abolished the relaxant phase of the response, whereas 3.10(-6) M indomethacin potentiated it. In uridine triphosphate-precontracted segments, there was not a net reduction in tone under 5-HT at 3.10(-9) to 3.10(-8) M, but further contraction appeared at higher concentrations. The presence of 10(-5) M L-NA significantly increased the contraction to 5-HT, but 3.10(-6) M indomethacin did not significantly reduce it. Endothelial lesion reduced by about 50% the contractile response Of L-NA-treated arteries to 5-HT; and conversely, endothelial lesion increased approximately twofold the contraction of indomethacin-treated arteries to 5-HT. We conclude that 5-HT causes the release from the endothelium of two vasoactive factors, one of which is probably the vasodilator nitric oxide, but the size of the relaxation may depend on the prevailing level of nitric oxide synthase activation. The second factor is a cyclooxygenase-dependent contractile agent, However, the contraction to 5-HT was not modified by the presence of the thromboxane synthase inhibitor CGS 13080 (10(-4)M), suggesting that thromboxane A(2) is not the main contractile agent released.