Urocortin-induced endothelium-dependent relaxation of rat coronary artery:: role of nitric oxide and K+ channels

1 The mechanisms underlying the vasodilator response to urocortin are incompletely understood. The present study was designed to examine the role of endothelial nitric oxide and Ba2+-sensitive K+ channels in the endothelium-dependent component of urocortin-induced relaxation in the rat left anterior descending coronary artery. 2 Urocortin induced both endothelium-dependent and -independent relaxation with respective pD(2) of 8.64 +/- 0.03 and 7.90 +/- 0.10. Removal of endothelium reduced the relaxing potency of urocortin. In rings pretreated with 10-4 m N-G-nitro-L-arginine methyl ester, 10(-5) m methylene blue or 10(-5) m ODQ, the urocortin-induced relaxation was similar to that observed in endothelium-denuded rings. L-Arginine (5 x 10(-4) m) antagonized the effect of N-G-nitro-L-arginine methyl ester. 3 The relaxant response to urocortin was reduced in endothelium-intact rings preconstricted by 3.5 x 10(-2) m K (+) and abolished when extracellular K (+) was raised to 5 x 10(-2) m. Pretreatment with 10-4 M BaCl2 significantly inhibited urocortin-induced relaxation. Combined treatment with 10(-4) M BaCl2 Plus 10(-4) m N-G-nitro-L-arginine methyl ester did not cause further inhibition. In urocortin (10(-8) m)-relaxed rings, BaCl2 induced concentration-dependent reversal in vessel tone. Tertiapin-Q (10(-6) M) also attenuated urocortin-induced relaxation. In contrast, BaCl2 did not alter urocortin-induced relaxation in endothelium-denuded rings. 4 In endothelium-denuded rings, hydroxylamine- and nitroprusside-induced relaxation was inhibited by 10(-4) m BaCl2, but not by 10(-6) m tertiapin-Q. 5 The endothelium of the coronary artery was moderately stained with the antiserum against urocortin. 6 Taken together, the present results indicate that the urocortin-induced endothelium-dependent relaxation of rat coronary arteries is likely attributable to endothelial nitric oxide and subsequent activation of Ba2+- or tertiapin-Q-sensitive K+ channels. The urocortin-induced endothelium-dependent relaxation appears to be mediated by cyclic GMP-dependent mechanisms.