Vasodilator action of the isopropyl ester of palmitoyl carnitine in the rat coronary circulation and mesenteric vascular bed.
The vasodilator action of the isopropyl ester of palmitoyl carnitine (P1Pi) has been examined in perfused rat hearts and mesenteric vessels. The coronary vasodilator effect P1Pi was not significantly inhibited by flurbiprofen (10 microM), BW755C (10 microM), glibenclamide (10 microM) or the bradykinin B2 receptor antagonist D-Arg0[Hyp3,Thi5,8,D-Phe7]bradykinin (1 microM), indicating that the action of P1Pi is not mediated via arachidonic acid metabolites, ATP-dependent K+ channels or bradykinin B2 receptors. L-NG-Nitro arginine (100 microM) did not inhibit the vasodilator action of P1Pi whilst superoxide dismutase (20 and 50 U.ml-1) attenuated its vasodilator action. Methylene blue (10 microM) caused inhibition in three out of four hearts, while haemoglobin (1 microM) caused an irreversible inhibition of the action of P1Pi which was associated with a depression of myocardial contractility. In air-damaged mesenteric vascular beds the vasodilator action of P1Pi was not attenuated, whilst that of acetylcholine was abolished. In K(+)-depolarised mesenteric vascular beds the constrictor action of Ca2+ was attenuated by P1Pi. Therefore the vasodilator effect of P1Pi appears to be the result of a direct effect on smooth muscle.
Department of Pharmacy and Pharmacology, University of Bath, Avon, UK.
D N
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Criddle
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M
Rad-Niknam
G H
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Dewar
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B
Woodward
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D010172:Palmitoylcarnitine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D015221:Potassium Channels; D018002:Receptors, Bradykinin; D014665:Vasodilator Agents; C088214:palmitoylcarnitine isopropyl ester; D010172:Palmitoylcarnitine; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D011188:Potassium; D002118:Calcium