Evidence against the involvement of cytochrome P450 metabolites in endothelium-dependent hyperpolarization of the rat main mesenteric artery

The Journal of Physiology
B Vanheel, J Van de Voorde

Abstract

1. The influence of different inhibitors of cytochrome P450 mono-oxygenase on the endothelium-dependent and -independent hyperpolarization in the isolated rat main mesenteric artery was investigated. 2. Application of acetylcholine (ACh; 1 microM) for 10 min evoked an endothelium-dependent peak hyperpolarization of about 18 mV followed by a partial recovery to a level 7 mV more negative than the resting value (-50.2 +/- 0.5 mV). 3. Proadifen (30 microM) completely and reversibly inhibited the ACh-induced hyperpolarization. Conversely, the imidazole antimycotics clotrimazole (30 microM) and miconazole (100 microM) had less effect on the peak endothelium-dependent hyperpolarization. The suicide substrate inhibitors 17-octadecynoic acid (17-ODYA; 5 microM) and 1-aminobenzotriazole (1-ABT; 2 mM) did not significantly influence endothelium-dependent hyperpolarization. 4. The endothelium-independent hyperpolarization (16 mV) evoked by leveromakalim (300 nM) was completely inhibited by proadifen as well as by clotrimazole and miconazole but was not affected by 17-ODYA or 1-ABT. 5. These results do not support the view that the ACh-induced endothelium-dependent hyperpolarization in the rat mesenteric artery is mediated by cytochrome P4...Continue Reading

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