and Purpose-Endothelin-1 (ET) has been shown to be involved in human pathological conditions, but its physiological function remains to be elucidated. The aim of this work was to assess whether endothelium-derived ET was involved in the overall responsiveness of freshly isolated human pial arteries. Methods-Samples of cerebral cortex, otherwise discarded, were obtained during tumor or epileptic lesion resections (nϭ10 donors). Arterial segments were isolated and mounted on a microvessel

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... . Results-Inhibition of nitric oxide (NO) formation with N -nitro-L-arginine (L-NA, 100 mol/L) increased basal tone by 7Ϯ1%E max (nϭ5). This increase in tone was fully abolished in the presence of BQ123 (1 mol/L; ET A receptor antagonist, PϽ.05) but potentiated by a subthreshold concentration of exogenous ET (1 nmol/L; 33Ϯ8%E max ; PϽ.05). In the presence of L-NA, serotonin (10 mol/L)-induced tone was doubled compared with the control response (PϽ.05) but reduced by 90% in the presence of BQ123 (PϽ.05). In the absence of L-NA, BQ123 prevented serotonin-induced tone (nϭ3). Oxymetazoline, a selective ␣ 2 -adrenergic receptor agonist, induced an endothelium-dependent relaxation of preconstricted human pial arteries. The relaxation was partially sensitive to NO synthase inhibition and fully prevented by the addition of ET, whereas substance P-induced relaxation was preserved. Glibenclamide (1 mol/L), an inhibitor of ATP-sensitive K ϩ channels and tetraethylammonium (1 mmol/L), an inhibitor of Ca 2ϩ -activated K ϩ channels had no effect on oxymetazoline-induced relaxation. Conclusions-The results of this study suggest first that ET is involved in the tonic response induced by NO synthase inhibition; second, part of the contractile response induced by serotonin is endothelium-dependent and sensitive to BQ123; and third, the data suggest that activation of ␣ 2 -adrenergic receptors generated an endothelium-dependent relaxation that was selectively inhibited by exogenous ET. (Stroke. 1998;29:175-180.) Key Words: endothelins Ⅲ endothelium Ⅲ nitric oxide synthase Ⅲ pial arteries E ndothelin-1 is a potent endothelium-derived constricting