Differential impairment of vasodilator responsiveness of peripheral resistance and conduit vessels in humans with atherosclerosis

The purpose of this study was to assess the effect of atherosclerosis on the regulation of limb blood flow. To examine this issue, the reactivity of resistance and conduit vessels was evaluated in 11 patients with peripheral atherosclerotic disease and six control subjects. Responsiveness of resistance vessels was measured by venous occlusion plethysmography. Responsiveness of conduit vessels was determined by quantitative angiography to measure the diameter of the superficial femoral artery. To distinguish endothelium-dependent vasodilation from that caused by direct smooth muscle relaxation, each participant received intra-arterial infusions of methacholine and nitroprusside, respectively. Flow-mediated dilation of the superficial femoral artery was determined during reactive hyperemia. Vasoconstrictor function was determined by the infusion of phenylephrine. Methacholine reduced calf vascular resistance in the control subjects but not in the patients with atherosclerosis (-64 ± 11% versus 6 ± 18%, p < 0.01). Nitroprusside decreased calf vascular resistance comparably in each group (-51 ± 5% versus -42 ± 4%, p = NS). The vasoconstrictor effect of phenylephrine was similar in each group (105 ± 30% versus 108 ± 22%, p = NS). In the superficial femoral artery, the vasodilator responses to both methacholine (20 ± 4% versus 1 ± 4%, p < 0.05) and nitroprusside (19 ± 4% versus 5 ± 4%, p < 0.05) were blunted in the atherosclerotic patients as was the vasoconstrictive response to phenylephrine (-15 ± 1% versus -1 ± 5%, p < 0.05). Reactive hyperemia induced a fivefold increase in calf blood flow in both control subjects (1.6 ± 0.2 to 11.1 ± 2.9 ml/100 ml/min, p < 0.05) and atherosclerotic patients (2.2 ± 0.3 to 10.0 ± 1.5 ml/100 ml/min, p < 0.05). During this flow augmentation, the superficial femoral artery dilated in control subjects (7.5 ± 0.8 to 8.2 ± 0.3 mm, p < 0.05) but not in atherosclerotic patients (6.0 ± 0.5 to 6.1 ± 0.5 mm, p = NS). Therefore, in humans with peripheral atherosclerosis, endothelium-dependent vasodilation in resistance vessels is impaired. Atherosclerotic conduit vessels are essentially unresponsive to vasodilator and vasoconstrictor stimuli, implicating functional abnormalities intrinsic to the vascular smooth muscle. These disturbances in vasomotor control may adversely affect blood flow regulation in humans with peripheral atherosclerosis and contribute to symptoms of claudication that occur in this disorder.