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https://hdl.handle.net/2440/8819
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Type: | Journal article |
Title: | The effects of perhexiline on the rat coronary vasculature |
Author: | Kennedy, J. Mohan, P. Pelle, M. Wade, S. Horowitz, J. |
Citation: | European Journal of Pharmacology, 1999; 370(3):263-270 |
Publisher: | ELSEVIER SCIENCE BV |
Issue Date: | 1999 |
ISSN: | 0014-2999 1879-0712 |
Statement of Responsibility: | Jennifer A. Kennedy, Puneet Mohan, Maria A. Pelle, Steven R. Wade, John D. Horowitz |
Abstract: | The predominant site and mechanism(s) of perhexiline-induced coronary vasodilatation were investigated in the rat heart. Perhexiline was more potent in the Langendorff perfused heart than in the left anterior descending coronary artery (EC50; 0.27 microM, confidence limits 0.19-0.39: 2.7 microM, 2.0-3.4, respectively). Selective endothelial inactivation with Triton X-100 in the perfused heart, reduced the response to perhexiline 1 microM (76+8% to 30+3% of control). 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) 3 microM, Nomega-nitro-L-arginine 100 microM, or a combination of the latter with indomethacin 10 microM, had no significant effect on responses to perhexiline in the perfused heart. Unlike bradykinin-induced vasodilatation, responses to perhexiline were not inhibited by tetrabutylammonium 1 mM, or charybdotoxin 20 nM. SKF525A 5 microM inhibited both perhexiline and bradykinin responses, while apamin 1 microM and glibenclamide 3 microM inhibited neither. Perhexiline exerts partially endothelium-dependent coronary vasodilator effects in the rat, predominantly on small coronary arteries, which appear to be independent of nitric oxide (NO), prostacyclin and the endothelium-derived hyperpolarising factor (EDHF) released by bradykinin. |
Keywords: | Muscle, Smooth Coronary Vessels Heart Ventricles Animals Rats Nitroprusside Nitric Oxide Octoxynol Perhexiline Epoprostenol Vasodilator Agents Biological Factors Perfusion Dose-Response Relationship, Drug Drug Interactions Male In Vitro Techniques |
DOI: | 10.1016/S0014-2999(99)00106-5 |
Published version: | http://dx.doi.org/10.1016/s0014-2999(99)00106-5 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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