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. doi: 10.1016/j.vph.2007.05.003. Epub 2007 Jun 2.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic
  • Cyclic GMP / metabolism*
  • Dose-Response Relationship, Drug
  • Guanylate Cyclase / antagonists & inhibitors
  • In Vitro Techniques
  • Light
  • Male
  • Nitric Oxide / metabolism
  • Nitric Oxide Donors / administration & dosage
  • Nitric Oxide Donors / pharmacology*
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / pharmacology*
  • Phenylephrine
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels, Calcium-Activated / drug effects*
  • Potassium Channels, Calcium-Activated / metabolism
  • Potassium Chloride
  • Rats
  • Rats, Wistar
  • Ruthenium / pharmacology*
  • Vasodilation / drug effects*

Substances

  • Nitric Oxide Donors
  • Organometallic Compounds
  • Potassium Channel Blockers
  • Potassium Channels, Calcium-Activated
  • Phenylephrine
  • Nitric Oxide
  • Potassium Chloride
  • Ruthenium
  • Guanylate Cyclase
  • Cyclic GMP