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CHARACTERIZATION OF DOCOSAHEXAENOIC ACID (A “FISH OIL”) ON VASOMOTOR RESPONSES IN RAT SMALL MESENTERIC RESISTANCE ARTERIES
  1. R Limbu,
  2. AJ McNeish
  1. ICMR and School of Pharmacy, University of Reading

Abstract

Diets high in omega-3 fish oils improve cardiovascular health. Supplementation studies demonstrate fish oils augment asodilation, normally by improvements in endothelial cell function. A recent postprandial study demonstrated that fish oils also improve endothelium-independent relaxation.

We therefore characterised the vasodilator mechanisms of a major constituent of fish oils, DHA in vascular relaxation of rat mesenteric artery.

Methods Rat mesenteric arteries were mounted in a wire myograph and pre-constricted with U46619; cumulative concentration response curves were then constructed for the vasodilator responses to DHA (100 nM-30 µM). Blockade of NO PGI2 and endothelium dependent hyperpolarization (EDH) vasodilator pathways on DHA induced relation were assessed using pharmacological blockade. The effect of DHA on endothelium-dependent and independent relaxation produced by ACh and NONOate, respectively, was also assessed.

Results DHA caused concentration-dependent relaxation unaffected by the inhibition of NOsynthase, or cyclooxygenase. Blockade of the K+ channels involved in the EDH pathway (SKCa, IKCa and BKCa) demonstrated inhibition of IKCa significantly reduced DHA mediated relaxation, the combined blockade of IKCa and BKCa caused further reduction. ACh-induced relaxation was unaffected by DHA, NONOate induced relaxation was potentiated.

Conclusions DHA produces vasodilation at concentrations relevant to the postprandial human plasma concentration (1–30 µM). This was not affected by inhibition of two endothelium-dependent vasodilator pathways (NO and PGI2) but block of EDH attenuated vasodilation. Endothelium-independent relaxation to NONOate was also potentiated. Thus relaxation produced by DHA is partially mediated by EDH, the mechanism underlying residual relaxation is unknown, but consistent with an effect on smooth muscle.

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