Bayram Zeliha, Golbasi Ilhan, Ozdem Sadi S
Department of Pharmacology, Akdeniz University, Medical Faculty, Antalya, Turkey.
Regul Pept. 2010 Apr 9;161(1-3):92-6. doi: 10.1016/j.regpep.2009.12.023. Epub 2010 Jan 14.
We investigated the effects of adrenomedullin (ADM) and the role(s) of cyclooxygenase, nitric oxide (NO) synthase and potassium channels in the effects of ADM in human internal thoracic artery (ITA) rings. Samples of redundant ITA rings were suspended in organ baths and isometric tension was continuously recorded. ADM (10(-10)-10(-7)M) produced concentration-dependent relaxation responses in ITA rings precontracted by phenylephrine. The relaxant responses to ADM were significantly higher in endothelium-intact than denuded preparations. Incubation of ITA rings with indomethacin (10(-5)M) did not cause a significant decrease in relaxant responses to ADM, while 10(-4)M of N(omega)-nitro-L-arginine methyl ester caused a significant decrease. Both specific guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (5x10(-5)M) and ADM receptor antagonist ADM((22-52)) (10(-7)M) also caused significant decreases in relaxant responses to ADM. Neither 4-aminopyridine (5mM) nor glibenclamide (10(-5)M) caused significant alterations in vasodilatory effect of ADM. ADM-induced relaxation was significantly blunted by both charybdotoxin and apamin. The present study provided pharmacological evidence about the functional relaxant effect of ADM in human ITA preparations. The findings suggested that both Ca(2+)-activated potassium channels and endothelium, through release of NO play a major role in ADM-induced relaxations in isolated human ITA preparations.
我们研究了肾上腺髓质素（ADM）的作用以及环氧化酶、一氧化氮（NO）合酶和钾通道在ADM对人胸廓内动脉（ITA）环作用中的作用。将多余的ITA环样本悬挂在器官浴槽中，并连续记录等长张力。ADM（10⁻¹⁰ - 10⁻⁷M）在由去氧肾上腺素预收缩的ITA环中产生浓度依赖性的舒张反应。在内皮完整的制剂中，对ADM的舒张反应明显高于去内皮的制剂。用吲哚美辛（10⁻⁵M）孵育ITA环不会导致对ADM的舒张反应显著降低，而10⁻⁴M的N（ω）-硝基-L-精氨酸甲酯会导致显著降低。特异性鸟苷酸环化酶抑制剂1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（5×10⁻⁵M）和ADM受体拮抗剂ADM（(22 - 52)）（10⁻⁷M）也会导致对ADM的舒张反应显著降低。4-氨基吡啶（5mM）和格列本脲（10⁻⁵M）均未引起ADM血管舒张作用的显著改变。ADM诱导的舒张反应被蝎毒素和蜂毒明肽均显著减弱。本研究提供了关于ADM在人ITA制剂中功能性舒张作用的药理学证据。研究结果表明，Ca²⁺激活的钾通道和内皮通过释放NO在分离的人ITA制剂中ADM诱导的舒张反应中起主要作用。
