title: 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 Ba(2+)-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 (5x10(-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 3.5x10(-2) M K(+) and abolished when extracellular K(+) was raised to 5x10(-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. 4. 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. 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 Ba(2+)- or tertiapin-Q-sensitive K(+) channels. The urocortin-induced endothelium-dependent relaxation appears to be mediated by cyclic GMP-dependent mechanisms.
authors.affiliation: Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. yu-huang@cuhk.edu.hk
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Franky Leung
authors.initials: FL
authors.lastname: Chan
authors.forename: Chi-Wai
authors.initials: CW
authors.lastname: Lau
authors.forename: Suk-Ying
authors.initials: SY
authors.lastname: Tsang
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: He
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Chen
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yao
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000032:analysis / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000032:analysis / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054832:Urocortins; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D018696:Neuroprotective Agents; D015221:Potassium Channels; D054832:Urocortins; D009569:Nitric Oxide; D003346:Corticotropin-Releasing Hormone