CARDIAC, CORONARY AND PERIPHERAL VASCULAR EFFECTS OF ACETYL GLYCERYL ETHER PHOSPHORYL CHOLINE IN THE ANESTHETIZED DOG

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 232  (1) , 156-162
Abstract
Acetyl glyceryl ether phosphoryl choline (AGEPC) is a potent vasodilator, platelet activator and inflammatory agent. The cardiac and peripheral vascular effects of AGEPC were assessed in anesthetized dogs in order to gain additional insight into the mechanism of action of this lipid. Injection of AGEPC (0.1-3.2 .mu.g) directly into the femoral vasculature produced a dose-related vasodilation in the innervated and sympathetically denervated hindlimb. Vasodilator responses in the denervated limb were at least as great as those in the innervated limb, which indicates that the response is not due to inhibition of sympathetic vasoconstrictor tone. Vasodilator reponses to AGEPC (1 .mu.g) were not significantly affected by theophylline (5 mg/kg), indomethacin (5 mg/kg) or BW755C [3-amino-1-m-trifluoromethylphenyl-2-pyrazoline] (10 mg/kg), which implies that the effect is independent of purinergic P1 receptors, cyclooxygenase products and lipoxygenase products. Intracoronary injection of AGEPC (0.032-3.2 .mu.g) reduced blood pressure, myocardial contractile force and coronary blood flow in a dose-related manner. Coronary vascular resistance was unchanged. Intracoronary injection of another activator of platelets, ADP (10 .mu.g), increased blood flow. Responses of blood pressure, heart rate, contractile force and coronary flow to AGEPC were not affected by bilateral vagotomy or hexamethonium, which indicates that they are independent of reflexive mechanisms. Indomethacin attenuated the hypotension and coronary flow reductions to AGEPC. BW755C reduced the hypotensive response. Mechanical reduction of coronary flow by 30-40% did not affect blood pressure, heart rate or contractile force, which suggests that AGEPC-induced changes are not secondary to flow reduction. Evidently AGEPC produces direct myocardial depression and distinct effects on the coronary and femoral vasculature. The peripheral vascular effects are independent of the autonomic nervous system, purinergic mechanisms and arachidonic acid metabolites, whereas some coronary effects may be mediated through metabolites of arachidonic acid.