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

Abstract

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 λ > 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 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 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/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 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.