The effects of perhexiline on the rat coronary vasculature.
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.
Kennedy
J A
JA
Cardiology Unit, University of Adelaide, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia. jkennedy@tqehsmtp.tqeh.sa.gov.au
Mohan
P
P
Pelle
M A
MA
Wade
S R
SR
Horowitz
J D
JD
D000818:Animals; D001685:Biological Factors / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D011464:Epoprostenol / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D017830:Octoxynol / Q000494:pharmacology; D010477:Perfusion; D010480:Perhexiline / Q000494:pharmacology*; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology*
D001685:Biological Factors; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009599:Nitroprusside; D009569:Nitric Oxide; D017830:Octoxynol; D011464:Epoprostenol; D010480:Perhexiline