Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans.

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 < 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. (J. Clin. Invest. 1990. 86:228-234.)

Arterial stiffness or endothelial dysfunction as a surrogate marker of vascular risk

“…Resistance vessel function in the forearm is assessed by strain-gauge venous impedance plethysmography. This methodology examines the change in forearm blood flow in response to direct intra-arterial (brachial artery) administration of agonists (62). This technique is excellent for acute interventions with repeated measurements.…”

Endothelial dysfunction and hypertension in aging

“…16,17 Under conditions of BH 4 deficiency, electron flow from the reductase domain to the oxidase domain is diverted to molecular oxygen rather than to L-arginine, a substrate of NO, leading to eNOS uncoupling. In this condition, uncoupled eNOS produces superoxide rather than NO.…”

“…8 A great number of studies have shown that aging and hypertension are associated with impairment of endothelium-dependent vascular relaxation in coronary, forearm and renal arteries, and endothelial dysfunction, which is involved in the development of atherosclerosis, was found to increase the risk of cardiovascular and cerebrovascular diseases. [9][10][11][12][13][14][15][16][17] It is expected that improvement or augmentation of endothelial function will prevent the development of atherosclerosis, resulting in reduction in cardiovascular and cerebrovascular events.…”

Atorvastatin improves the response to sildenafil in hypercholesterolemic men with erectile dysfunction not initially responsive to sildenafil

“…It has been reported that impaired endothelium-dependent and -independent vasodilation in patients with ED is similar to that of patients with hypercholesterolemia. 40 In addition, some studies have shown that hypercholesterolemia results in an increase in sympathetic activity. 41 Current medical treatments for ED, such as PDE5 inhibitors, are palliative.…”