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DECREASED VASODILATION INDUCED BY A NEW NITRIC OXIDE DONOR IN TWO KIDNEY, ONE CLIP HYPERTENSIVE RATS IS DUE TO IMPAIRED K + CHANNEL ACTIVATION
Author(s) -
Bonaventura Daniella,
Oliveira Fabiana S,
Da Silva Roberto S,
Bendhack Lusiane M
Publication year - 2005
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2005.04215.x
Subject(s) - iberiotoxin , glibenclamide , apamin , nitric oxide , vasodilation , channel blocker , charybdotoxin , chemistry , endocrinology , medicine , potassium channel , calcium , diabetes mellitus
SUMMARY 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 µmol/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 µmol/L), 4‐aminopyridine (blocks K V ; 1 mmol/L) and the small conductance K Ca channel blocker apamin (1 µmol/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.