Vasorelaxation induced by the new nitric oxide donor cis-[Ru(Cl)(bpy)₂(NO)](PF₆) is due to activation of K_Ca by a cGMP-dependent pathway

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• 作者：Claure N. Lunardi ; Juliana A. Vercesi ; Roberto S. da Silva ; Lusiane M. Bendhack
• 关键词：Ruthenium complex ; Nitric oxide ; NO donor ; Vasorelaxation ; K⁺ channels
• 刊名：Vascular Pharmacology
• 出版年：2007
• 期刊代码：59_15371891
• 类别：pha
• 出版时间：August-September 2007
• 卷：47
• 期：2-3
• 页码：139-144
• 文件大小：218 K

摘要

We investigated the effects of selective K⁺ channel blockers and guanylyl cyclase inhibitor on the rat aorta relaxation induced by the new NO donor cis-[Ru(Cl)(bpy)₂(NO)](PF₆) (RUNOCL), following endothelium removal. NO release from RUNOCL was obtained by photo-induction using a visible light system λ > 380 nm. RUNOCL induced relaxation of phenylephrine contracted aortic rings under light with the maximum effect (ME) of 101.2 ± 3.7%and pD₂: 6.62 ± 0.16 (n = 7), but not in the absence of light. Relaxation stimulated with RUNOCL was also studied on 60 mM of KCl-contracted arteries or after incubation with the non-selective K⁺ channel blocker (1 mM TEA) or the selective K⁺ channel blockers (3 μM glibenclamide (K_ATP), 1 mM 4-aminopyridine (K_V, 4-AP), 1 μM apamin (SK_Ca-APA) or 0.1 μM iberiotoxin (BK_Ca IBTX). Relaxation induced by RUNOCL was lower in KCl-contracted aortic rings with ME of 68.6 ± 10.0%and pD₂: 3.92 ± 0.60 (n = 4). As compared to Phe-contracted arteries the potency of RUNOCL in inducing rat aorta relaxation was reduced by K⁺ channel blockers as demonstrated by the pD₂ values from 6.62 ± 0.16 (n = 7) (control) to (TEA: 5.32 ± 0.108, n = 5; IBTX: 5.63 ± 0.02 (n = 5), APA: 5.73 ± 0.13 (n = 5)). But the ME was reduced only by IBTX (60.7 ± 3.4%). 4-AP and glibenclamide had no effect on the relaxation induced by RUNOCL. The aortic tissue cGMP content increased with RUNOCL under light irradiation from 63.13 ± 0.45 fmol/μg to 70.56 ± 4.64 fmol/μg of protein (n = 4) and the inhibition of guanylyl cyclase with ODQ reduced the ME: 30.1 ± 1.6%and pD₂: 6.35 ± 0.05 (n = 4). Our results suggest that the NO released by photo-induction from RUNOCL induces rat aorta relaxation by activation of K_Ca by a cGMP-dependent pathway.