Eicosapentaenoic Acid Inhibits Endothelium-Dependent Relaxation to Acetylcholine in Guinea Pig Coronary Resistance Vessels

Linda Lee, R. Clinton Webb, Bertram Pitt

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Abstract

Dietary supplementation with eicosapentaenoic acid (EPA) alters arachidonate metabolism. This study characterizes the effect of dietary EPA on endothelium-dependent vasodilation to acetylcholine (ACH) and ATP in guinea pig coronary resistance vessels. Guinea pigs were fed standard chow (n = 6), standard chow + sesame seed oil (n = 6), or standard chow + menhaden fish oil (17% EPA; n = 6). Coronary vasodilations were examined in the isolated, potassium-arrested heart utilizing a modified Langendorff preparation. Coronary vessels were constricted with prostaglandin F and relaxed with ACH (5.5 × 109-106 moles) or ATP (1010-107 moles). Endothelium-dependent dilations to ACH, but not ATP, were attenuated by dietary supplementation with EPA. To assess the role of the endothelium in modulating vascular responses to agonists following dietary manipulation, the perfusate was stimulated by electrolysis (9 V, 4 Hz, 2 msec) in order to generate free radicals, which we have shown to preferentially damage the endothelium. After endothelial damage, responses to ACH, ATP, and nitroprusside were similar between the dietary groups. In an additional group of standard diet animals (n = 6) experiments were performed to assess the role of prostanoid metabolism in affecting coronary vascular reactivity. Perfusion of hearts with indomethacin (14 μM) reduced endothelium-dependent vasodilations to ACH (5.5 × 109-105 moles), but not to ATP (1010-107 moles). After endothelial damage, infusion of ACH resulted in vasoconstriction, whereas vasodilation responses to ATP were absent. We conclude that dietary supplementation with EPA inhibits endothelium-dependent dilations to ACH in guinea pig coronary microvessels. These diet-related differences in vascular reactivity may be related to the fish-oil-induced alteration of vasodilator prostaglandin metabolism. In the coronary bed, different endothelial factors appear to mediate relaxation to ACH and ATP.

Original languageEnglish (US)
Pages (from-to)466-471
Number of pages6
JournalProceedings of the Society for Experimental Biology and Medicine
Volume200
Issue number4
DOIs
StatePublished - Sep 1992
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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