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

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 Ba 2+ ‐sensitive K + channels in the endothelium‐dependent component of urocortin‐induced relaxation in the rat left anterior descending coronary artery. 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 (5×10 −4   M ) antagonized the effect of N G ‐nitro‐ L ‐arginine methyl ester. 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 BaCl 2 significantly inhibited urocortin‐induced relaxation. Combined treatment with 10 −4   M BaCl 2 plus 10 −4   M N G ‐nitro‐ L ‐arginine methyl ester did not cause further inhibition. In urocortin (10 −8   M )‐relaxed rings, BaCl 2 induced concentration‐dependent reversal in vessel tone. Tertiapin‐Q (10 −6   M ) also attenuated urocortin‐induced relaxation. In contrast, BaCl 2 did not alter urocortin‐induced relaxation in endothelium‐denuded rings. In endothelium‐denuded rings, hydroxylamine‐ and nitroprusside‐induced relaxation was inhibited by 10 −4   M BaCl 2 , but not by 10 −6   M tertiapin‐Q. The endothelium of the coronary artery was moderately stained with the antiserum against urocortin. 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 Ba 2+ ‐ or tertiapin‐Q‐sensitive K +  channels. The urocortin‐induced endothelium‐dependent relaxation appears to be mediated by cyclic GMP‐dependent mechanisms.British Journal of Pharmacology (2002) 135 , 1467–1476; doi: 10.1038/sj.bjp.0704587