Effect of palmitoyl carnitine isopropyl ester on the actions of BAY K 8644 and norepinephrine in the perfused rat heart.
We examined the actions of the isopropyl ester of palmitoyl carnitine (P1Pi), a novel vasodilator compound, on coronary constriction mediated by the calcium channel activator BAY K 8644 and positive inotropic responses mediated by norepinephrine (NE) and low sodium perfusion in perfused rat hearts. Langendorff-perfused hearts were given bolus doses of BAY K 8644 or NE. The effects of P1Pi or atenolol on perfusion pressure, heart rate (HR), and developed tension changes induced by these agents were studied. In other experiments, low-sodium perfusion was used to manipulate sodium-calcium exchange in the presence and absence of P1Pi. P1Pi inhibited the coronary constrictor action of BAY K 8644 and also produced a selective inhibition of the inotropic but not the chronotropic action of NE. These effects of P1Pi were not associated with any depression of basal myocardial contractility. P1Pi did not affect the inotropic or coronary constrictor responses induced by low-sodium perfusion. The effects of P1Pi on the responses induced by BAY K 8644 and NE indicate that P1Pi inhibits activated L-type calcium channels while having no effect on sodium-calcium exchange. These effects may be related to the charged nature of this amphiphilic compound.
Reeves
K A
KA
School of Pharmacy & Pharmacology, University of Bath, England.
Rad-Niknam
M
M
Dewar
G H
GH
Woodward
B
B
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010172:Palmitoylcarnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D002120:Calcium Channel Agonists; D015220:Calcium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C088214:palmitoylcarnitine isopropyl ester; D010172:Palmitoylcarnitine; D001262:Atenolol; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D012964:Sodium; D002118:Calcium; D009638:Norepinephrine