Enhanced alpha-adrenergic vasoconstriction by n-3 fatty acids in conscious dogs

Abstract

The effect of dietary fish oil supplementation on cardiac function and the pressor response to selective agonists of postjunctional alpha 1- and alpha 2-adrenoceptors was investigated in chronically instrumented dogs (n = 12). Following ganglionic, cholinergic, and beta-adrenergic blockade, dose responses to phenylephrine (0.3-1.2 micrograms/kg iv), a selective alpha 1-adrenoceptor agonist, and azepexole (B-HT 933, 5-20 micrograms/kg iv), a selective alpha 2-adrenoreceptor agonist, were obtained in conscious dogs. Fish oil capsules containing eicosapentaenoic acid (1.12 g) and docosahexaenoic acid (480 mg) were administered orally twice daily for 1 wk, and dose-response curves were repeated. Dose-response curves were again obtained 1 wk after fish oil was discontinued. Fish oil supplementation resulted in significantly (P less than 0.05) increased arterial pressure at rest, and after autonomic nervous system blockade there was an increase in peripheral vascular resistance. Cardiac output was reduced in fish oil-treated dogs during autonomic nervous system blockade. The pressor response to selective alpha 1- and alpha 2-adrenoceptor stimulation was increased secondary to elevated peripheral vascular resistance. Hemodynamics and exaggerated vascular reactivity returned to control 1 wk after dietary fish oil was discontinued. The results of this study demonstrate that dietary fish oil supplementation produces an increase in arterial pressure via peripheral vasoconstriction and that the vascular response to alpha-adrenergic stimulation is exaggerated.