THE EFFECTS OF NOVEL VASODILATOR LONG-CHAIN ACYL CARNITINE ESTERS IN THE ISOLATED PERFUSED HEART OF THE RAT

The effects of palmitoyl carnitine (PC) and novel derivatives were examined on the isolated Langendorff perfused heart of the rat. Bolus injections of PC (1-330 nmol) produced coronary constriction accompanied by a cumulative irreversible depression of contractility. Prior storage of PC in chloroform containing 2% ethanol in heat-sealed ampoules resulted in production of the ethyl ester of the compound (PCE). This compound was isolated and also synthesized (P1E). In contrast to PC, both PCE and P1E exhibited potent vasodilator activity. Increasing the fatty acid chain length from palmitoyl to stearoyl resulted in a significant reduction in coronary dilator activity of the ester compound, whereas different ester groups did not affect the vasodilator action appreciably. Complete removal of the fatty acid chain abolished all vascular effects at the doses used. The vasodilatation produced by these acyl carnitine esters was comparable to that produced by several known vasodilator drugs including verapamil, cromakalim, amyl nitrate and iloprost; however, the duration of the vasodilator response was more prolonged with the carnitate derivatives.