Endothelial cytochrome P450 contributes to the acetylcholine-induced cardiodepression in isolated rat hearts

Acta Physiologica Scandinavica
P PagliaroD Gattullo

Abstract

Acetylcholine (ACh) is known to reduce the contractility of the heart by acting on myocardial muscarinic M2 receptors. ACh induces also an endothelial-dependent vasodilatation by causing the release of nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factors from the vascular endothelium. It has been proposed that ACh elicits a hyperpolarization of the coronary endothelial cells which may be accompanied by the activation of cytochrome P450 (CYP) and the resulting release of epoxyeicosatrienoic acids (EETs). The study aims at investigating whether endothelial CYP is involved in the cardiodepression by ACh. In isolated rat hearts, cardiodepression by ACh (i.e. 25-30% reduction of developed left ventricular pressure) was partially attenuated either by inhibition of CYP with 1-aminobenzotriazole (ABT) or by endothelial dysfunction obtained with Triton X-100. No attenuation of cardiodepression was seen after nitric oxide synthase and cyclooxygenase inhibition by L-nitro-arginine methyl ester and indomethacin, respectively. The results suggest that the negative inotropic effect of ACh depends not only on a direct myocardial effect but also on the endothelial CYP activation.

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Citations

Apr 24, 2009·Journal of Bioenergetics and Biomembranes·Giovanna LippeIrene Mavelli
Mar 29, 2005·Basic Research in Cardiology·J Vinten-JohansenF Kerendi
Sep 14, 2007·Journal of Bioenergetics and Biomembranes·Stefania ContessiIrene Mavelli

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