| 17602893 |
Lunardi CN, Vercesi JA, da Silva RS, Bendhack LM: Vasorelaxation induced by the new nitric oxide donor cis-[Ru (Cl)(bpy)(2)(NO)](PF (6)) is due to activation of K (Ca) by a cGMP-dependent pathway. Vascul Pharmacol. 2007 Aug-Sep;47(2-3):139-44. Epub 2007 Jun 2.
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)](PF (6)) (RUNOCL), following endothelium removal. NO release from RUNOCL was obtained by photo-induction using a visible light system lambda > 380 nm. RUNOCL induced relaxation of phenylephrine contracted aortic rings under light with the maximum effect (ME) of 101.2+/-3.7% and pD (2): 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 microM glibenclamide (K (ATP)), 1 mM 4-aminopyridine (K (V), 4-AP), 1 microM apamin (SK (Ca)-APA) or 0.1 microM iberiotoxin (BK (Ca) IBTX). Relaxation induced by RUNOCL was lower in KCl-contracted aortic rings with ME of 68.6+/-10.0% and pD (2): 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 pD (2) 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/microg to 70.56+/-4.64 fmol/microg of protein (n=4) and the inhibition of guanylyl cyclase with ODQ reduced the ME: 30.1+/-1.6% and pD (2): 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. |
6(0,0,1,1) |