Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans - PubMed (original) (raw)

Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans

M A Creager et al. J Clin Invest. 1990 Jul.

Abstract

The effect of hypercholesterolemia on vascular function was studied in humans. To eliminate the potential confounding effects of atherosclerosis, vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 111 +/- 7 mg/dl) and 13 patients with hypercholesterolemia (serum LDL cholesterol = 211 +/- 19 mg/dl, P less than 0.05). Each subject received intrabrachial artery infusions of methacholine, which releases endothelium-derived relaxant factor, and nitroprusside which directly stimulates guanylate cyclase in vascular smooth muscle. Maximal vasodilatory potential was determined during reactive hyperemia. Vasoconstrictive responsiveness was examined during intra-arterial phenylephrine infusion. Forearm blood flow was determined by venous occlusion plethysmography. Basal forearm blood flow in normal and hypercholesterolemic subjects was comparable. Similarly, reactive hyperemic blood flow did not differ between the two groups. In contrast, the maximal forearm blood flow response to methacholine in hypercholesterolemic subjects was less than that observed in normal subjects. In addition, the forearm blood flow response to nitroprusside was less in hypercholesterolemic subjects. There was no difference in the forearm vasoconstrictive response to phenylephrine in the two groups. Thus, the vasodilator responses to methacholine and nitroprusside were blunted in patients with hypercholesterolemia. We conclude that in humans with hypercholesterolemia, there is a decreased effect of nitrovasodilators, including endothelium-derived relaxing factor, on the vascular smooth muscle of resistance vessels.

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References

1. 1. Nature. 1987 May 21-27;327(6119):237-9 - PubMed
2. 1. Circulation. 1988 Dec;78(6):1421-30 - PubMed
3. 1. J Clin Invest. 1989 Feb;83(2):465-73 - PubMed
4. 1. Am J Physiol. 1989 Mar;256(3 Pt 1):C591-7 - PubMed
5. 1. Clin Sci (Lond). 1955 May;14(2):197-211 - PubMed

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