Comparative effects of the potassium channel openers cromakalim and pinacidil and the cromakalim analog U-89232 on isolated vascular and cardiac tissue.
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| Abstract |
ATP-sensitive potassium (K+ATP) channel openers such as cromakalim and pinacidil exhibit both potent vasodilatory and anti-ischemic properties. U-89232, a cyanoguanidine analog of cromakalim, has recently been found to exhibit myocardial protection during ischemia without altering in vivo hemodynamics. We examined the effects of U-89232, cromakalim and pinacidil in isolated vascular and cardiac tissue and tested whether glyburide, a KATP channel blocker, could antagonize their effects. All three compounds produced concentration-dependent relaxation in isolated vascular segments, with cromakalim being approximately 100-fold more potent than either pinacidil or U-89232. Glyburide completely antagonized the effects of pinacidil but merely blunted the effects of cromakalim and U-89232. In an isolated rabbit cardiac tissue preparation, U-89232 had little effect on maximum tension in cardiac muscle, whereas cromakalim and pinacidil significantly decreased maximum developed tension in a concentration-dependent manner. Glyburide effectively antagonized the effects of cromakalim and pinacidil in cardiac tissue. These data suggest that U-89232, although chemically related to cromakalim, possesses activity which is not common to known potassium channel openers.
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| Authors | N R Norman, C F Toombs, S A Khan, L V Buchanan, M G Cimini, J K Gibson, K D Meisheri, R J Shebuski |
| Journal | Pharmacology (Pharmacology) Vol. 49 Issue 2 Pg. 86-95 (Aug 1994) ISSN: 0031-7012 [Print] Switzerland |
| PMID | 7972325 (Publication Type: Comparative Study, Journal Article) |
| Chemical References |
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