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.
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.
Lunardi
Claure N
CN
Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP. 14.040-903 Ribeirão Preto, SP-Brazil.
Vercesi
Juliana A
JA
da Silva
Roberto S
RS
Bendhack
Lusiane M
LM
D000818:Animals; D001013:Aorta, Thoracic; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008027:Light; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D010656:Phenylephrine; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000378:metabolism; D011189:Potassium Chloride; D051381:Rats; D017208:Rats, Wistar; D012428:Ruthenium / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D020030:Nitric Oxide Donors; D009942:Organometallic Compounds; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D010656:Phenylephrine; D009569:Nitric Oxide; D011189:Potassium Chloride; D012428:Ruthenium; D006162:Guanylate Cyclase; D006152:Cyclic GMP