Role of Digital Artery Adrenoceptors in Raynaud's Disease

Abstract

Raynaud's disease is characterized by excessive cutaneous vasoconstriction in response to ambient cold. A functional disturbance in the local regulation of digital vasomotion has been proposed. The purpose of this study was to determine whether there is an alteration in the postjunctional adrenergic receptors in the digital circulation of patients with Raynaud's disease. Furthermore, we sought to determine whether this abnormality was responsible for the excessive cold-induced vasoconstriction in these patients. Finger blood flow was measured by strain-gauge venous occlusion plethysmography in 10 patients with Raynaud's disease and in 10 normal volunteers in a 22 °C room. Measurements of finger blood flow and mean systemic arterial pressure were made during intra-arterial infusions of the alpha1-adrenergic antagonist, prazosjn, or the alpha2-adrenergic antagonist, yohimbine, at room temperature and during local cooling of the hand. Basal finger blood flow in normal subjects was significantly greater than that of patients (8.6 ± 2.7 vs 1.7 ± 0.5 ml/100 ml per min; normal vs Raynaud's subjects; p < 0.05). In normal subjects, either prazosin or yohimbine induced dose-dependent increases in finger blood flow. The maximal increase in finger blood flow induced by prazosin was significantly greater than that in response to yohimbine (29.2 ± 10.1 vs 2.8 ± 2.1 ml/100 ml per min; prazosin vs yohimbine; p < 0.05). By contrast, in the Raynaud's patients, prazosin or yohimbine induced maximal increases in finger blood flow that were not significant (7.1 ± 1.8 vs 5.0 ± 2.2 ml/100 ml per min; prazosin vs yohimbine; p = NS). The response to prazosin in Raynaud's patients was significantly less than that of the normal volunteers ( p < 0.05). In normal subjects, during intra-arterial infusion of vehicle alone, cooling induced a 52.6 ± 5.8% reduction in finger blood flow. This cold-induced vasoconstriction was blunted, but not qualitatively altered, by either adrenergic antagonist. In the Raynaud's patients, during the intra-arterial infusion of the vehicle, cooling induced a 68.2 ± 7.8% reduction in finger blood flow. Infusion of either adrenergic antagonist blunted, but did not qualitatively alter, the response to cold. Finger blood flow is less in patients with Raynaud's disease than in normal subjects when studied in a 22 °C room. In normal subjects, postjunctional alpha1-adrenergic receptors appear to predominate in the control of digital vasoconstriction. Postjunctional alpha1- and alpha2- adrenoceptors play an equal role in adrenergic regulation of finger blood flow in patients with Raynaud's disease. In both normal and Raynaud's subjects, selective antagonism of alpha1- or alpha2-adrenergic receptors does not abolish local cold-induced vasoconstriction. Therefore, it is likely that a nonadrenergic mechanism contributes to local cold-induced vasoconstriction.