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

Abstract

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 pD2 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 NG-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 × 10-4 M) antagonized the effect of NG-nitro-L-arginine methyl ester. 3. The relaxant response to urocortin was reduced in endothelium-intact rings preconstricted by 3.5 × 10-2 M K+ and abolished when extracellular K+ was raised to 5 × 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 NG-nitro-L-arginine methyl ester did not cause further inhibition. In urocortin (10-3 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.