Decreased vasodilation induced by a new nitric oxide donor in two kidney, one clip hypertensive rats is due to impaired K+ channel activation

1. We studied the effect of the new compound trans-[RuCl([15]aneN(4))NO](2+) (15-ane) in denuded aortic rings of two kidney (2K) normotensive and two kidney, one clip (2K-1C) hypertensive rats. 2. The compound 15-ane releases nitric oxide (NO) when reduced by a catecholamine (noradrenaline). 3. Oxyhemoglobin (HbO(2)), an NO scavenger, completely abolished the effect of 15-ane in both 2K and 2K-1C rats, indicating that the relaxation is really due to NO release. 4. We tested the hypothesis that an impairment of K+ channels plays an important role in the vasodilation induced by 15-ane. 5. The selective inhibitor of soluble guanylyl-cyclase, namely 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ; 1 mu mol/L) reduced the relaxation induced by 15-ane. In 2K-1C rat aortic rings, ODQ reduced the maximum effect (E-max) of 15-ane, whereas in 2K rat aortic rings ODQ reduced E-max and pD(2) values to 15-ane. 6. The selective K+ channel blockers glibenclamide (blocks K-ATP; 3 mu mol/L), 4-aminopyridine (blocks K-V; 1 mmol/L) and the small conductance K-Ca channel blocker apamin (1 mu mol/L) reduced E-max and pD(2) values for 15-ane-induced relaxation responses of aortas from 2K rats. However, iberiotoxin, a blocker of large conductance K-Ca channels, reduced only the E-max to 15-ane. None of these K+ channel blockers had any effect on the relaxation induced by 15-ane of aortas from 2K-1C rats. 7. These data indicate that an impaired functional activity of K+ channels contributes to the deficient relaxation induced by the NO donor 15-ane in renal hypertensive 2K-1C rat aortas.