Contribution of arachidonic acid metabolites to reduced norepinephrine-induced contractions in hypercholesterolemic rabbit aortas

Journal of Cardiovascular Pharmacology
S L Pfister, W B Campbell

Abstract

Because alterations in the aortic metabolism of arachidonic acid and in vascular responsiveness occur in hypercholesterolemic rabbits, we hypothesized that an arachidonic acid metabolite may contribute to the regulation of vascular tone. Aortic contractions to norepinephrine were investigated in rabbits fed either standard chow or chow containing 2% cholesterol. In normal rabbits, norepinephrine (10(-6) M) elicited a 126 +/- 2% contraction compared with a 95 +/- 2% contraction in cholesterol-fed rabbits. The factor mediating the depressed response was endothelium-dependent because removal of the endothelium blocked the decrease in norepinephrine-induced contractions observed in the cholesterol-fed rabbits. The endothelium-derived factor was not nitric oxide, because blockade of nitric oxide synthase with nitro-L-arginine did not abolish the decreased response in the cholesterol-fed rabbits. Pretreatment of aortas with a cyclooxygenase inhibitor, indomethacin (10(-5) M) caused a slight decrease in the norepinephrine-induced contractions, suggesting that the factor could be a vasoconstrictor cyclooxygenase metabolite or a vasodilatory lipoxygenase or cytochrome P450 epoxygenase metabolite. Pretreatment with the thromboxane A2/pro...Continue Reading

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Citations

Jan 12, 2002·British Journal of Pharmacology·Victor E EsenabhaluWolfgang F Graier
Feb 10, 2010·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Phoebe A StapletonJefferson C Frisbee
Dec 30, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Nitin T AggarwalWilliam B Campbell
Jul 13, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Phoebe A StapletonJefferson C Frisbee

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