Non-esterified fatty acids impair endothelium-dependent vasodilation in rat mesenteric resistance vessels

Sainsbury, C., Sattar, N. , Connell, J., Hillier, C. and Petrie, J. (2004) Non-esterified fatty acids impair endothelium-dependent vasodilation in rat mesenteric resistance vessels. Clinical Science, 107(6), pp. 625-629.

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Abstract

Elevated circulating levels of NEFAs (non-esterified fatty acids) are associated with states of insulin resistance and increased risk of vascular disease. Previous animal and human studies have demonstrated NEFA-induced endothelial dysfunction of large conduit arteries, reversible by the antioxidant ascorbic acid. We therefore investigated the effect of NEFAs on carbachol-induced endothelium-dependent vasodilation of rat resistance arteries in vitro using the technique of wire myography. In addition, we investigated the effect of co-incubation of NEFAs and ascorbic acid. Cumulative concentration-response curves to carbachol (endothelium-dependent vasodilation) and SNAP (S-nitroso-N-acetyl-DL-penicillamine; endothelium-independent vasodilation) were constructed. Those to carbachol were repeated following a 30 min incubation with either oleic acid (10(-4) M) or palmitic acid (10(-4) M), demonstrating significant impairment of endothelium-dependent vasodilation with both [P < 0.05, comparison of pD(2) values (the negative log concentration of agonist required to effect a 50% response)]. A cumulative concentration-response curve to carbachol was repeated following co-incubation with palmitic acid (10(-4) M) and the antioxidant ascorbic acid (10(-5) M), demonstrating an abolition of the previously observed endothelial dysfunction induced by palmitic acid. There was no impairment of vasodilation to SNAP following NEFA incubation. We conclude that NEFAs directly impair endothelial function in rat resistance arteries via an increase in oxidative stress at the vascular endothelium.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sainsbury, Dr Christopher and Connell, Professor John and Petrie, Professor John and Sattar, Professor Naveed
Authors: Sainsbury, C., Sattar, N., Connell, J., Hillier, C., and Petrie, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences
Journal Name:Clinical Science
ISSN:0143-5221

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