Arachidonic acid induced coronary reactions and their inhibition by docosahexaenoic acid.
The objective of the present study was to further investigate the influence exerted by docosahexaenoic acid (DHA) on the coronary reactions induced in isolated perfused hearts of rats and guinea pigs by bolus doses of arachidonic acid (AA). As in previous studies, we found that AA produced a coronary constriction followed by a longer lasting dilatation. The present data demonstrate that a 5-min infusion of DHA at 0.17-0.68 microM caused a concentration-dependent inhibition of the AA-induced constriction. The vasodilatation determined by AA was also depressed, but only after about 30 min of a sustained DHA infusion. The precursor of AA, linoleic acid (LA), was also infused for about 30 min, and like DHA it inhibited the coronary reactions induced by AA. LA is not converted into AA by the isolated heart, but like DHA, was probably incorporated into the cells of the coronary vascular compartment. It is known that LA, administered "in vivo" to mammals, is converted into AA and increases the production of eicosanoids, whereas DHA does not follow this metabolic pathway. The incorporation of these essential polyunsaturated fatty acids by the isolated perfused heart would inhibit the cyclooxygenase in the coronary vessel walls, interfering with the generation of vasomotor metabolites from AA. We postulate that the systemic administration of DHA, by inhibiting the synthesis of a constrictor metabolite, could be beneficial in reducing the damage due to microvascular constriction in myocardial ischaemia.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004281:Docosahexaenoic Acids; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008297:Male; D051381:Rats; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019787:Linoleic Acid