Abstract

In the present study, endothelin (ET) agonists and receptor selective antagonists were used to characterize ET receptors mediating constriction in guinea pig mesenteric veins (250–300 μm diameter) in vitro. The contribution of ET-evoked vasodilator release to venous tone was also explored. Computer-assisted video microscopy was used to monitor vein diameter. Endothelin-1 (ET-1), endothelin-3 (ET-3), and sarafotoxin 6c (S6c) produced sustained concentration-dependent contractions with a rank order agonist potency of ET-1 = S6c > ET-3. Indomethacin (1 μM) andNϖ-nitro-l-arginine (100 μM) enhanced ET-1 and S6c responses. The ET_A selective antagonists BQ-610 (100 nM) and PD156707 (10 nM) shifted ET-1 concentration-response curves rightward and decreased maximal ET-1 responses, without changing S6c responses. The ET_Bselective antagonist BQ-788 (100 nM) shifted S6c responses rightward but produced no change in ET-1 responses. Combined application of BQ-788 and BQ-610 or BQ-788 and PD 156707 produced a rightward shift in ET-1 responses that was greater than shifts produced by BQ-610 or PD 156707 alone. In conclusion, smooth muscle in guinea pig mesenteric veins expresses ET_A and ET_B receptors coupled to contractile mechanisms. Activation of endothelial ET_Breceptors results in release of vasodilators, primarily nitric oxide.