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 (EC 50; 0.27 μM, confidence limits 0.19–0.39: 2.7 μM, 2.0–3.4, respectively). Selective endothelial inactivation with Triton X-100 in the perfused heart, reduced the response to perhexiline 1 μM (76+8% to 30+3% of control). 1 H-[1,2,4]Oxadiazolo[4,3- a]quinoxalin-1-one (ODQ) 3 μM, Nϖ-nitro- l-arginine 100 μM, or a combination of the latter with indomethacin 10 μM, 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 μM inhibited both perhexiline and bradykinin responses, while apamin 1 μM and glibenclamide 3 μM 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
