Role of digital artery adrenoceptors in Raynaud's disease.

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 degrees C room. Measurements of finger blood flow and mean systemic arterial pressure were made during intra-arterial infusions of the alpha 1-adrenergic antagonist, prazosin, or the alpha 2-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 degrees C room. In normal subjects, postjunctional alpha 1-adrenergic receptors appear to predominate in the control of digital vasoconstriction. Postjunctional alpha 1- and alpha 2-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 alpha 1- or alpha 2-adrenergic receptors does not abolish local cold-induced vasoconstriction. Therefore, it is likely that a nonadrenergic mechanism contributes to local cold-induced vasoconstriction.

Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus.

BACKGROUND: Endothelium-dependent vasodilation is abnormal in experimental models of diabetes mellitus. We postulated that abnormalities of endothelial function are also present in patients with insulin-dependent diabetes mellitus and may contribute to the pathogenesis of vascular disease in these individuals. METHODS AND RESULTS: Vascular reactivity was measured in the forearm resistance vessels of 15 patients with insulin-dependent diabetes mellitus and 16 age-matched normal subjects. No patient had hypertension or dyslipidemia. Each subject was pretreated with aspirin to inhibit endogenous production of prostanoids. Methacholine chloride (0.3 to 10 micrograms/min) was administered via the brachial artery to assess endothelium-dependent vasodilation. Sodium nitroprusside (0.3 to 10 micrograms/min) and verapamil (10 to 300 micrograms/min) were infused intra-arterially to assess endothelium-independent vasodilation; phenylephrine (0.3 to 3 micrograms/min) was administered to examine vasoconstrictor responsiveness. Forearm blood flow was determined by venous occlusion plethysmography, and dose-response curves were generated for each drug. Basal forearm blood flow in diabetic and normal subjects was comparable (2.6 +/- 0.2 versus 2.1 +/- 0.3 mL x 100 mL-1 x min-1, respectively; P = NS). The forearm vasodilative response to methacholine was less in diabetic than in normal subjects. At the highest dose of methacholine, the forearm blood flow increased 9.5 +/- 1.1 mL x 100 mL-1 x min-1 in diabetic subjects and 15.3 +/- 1.4 mL.100 mL-1 x min-1 in normal subjects (P < .01). The forearm blood flow responses to nitroprusside and verapamil and the forearm vasoconstrictor responses to phenylephrine were similar in diabetic and healthy subjects. In diabetic subjects, endothelium-dependent vasodilation correlated inversely with serum insulin concentration but not with glucose concentration, glycosylated hemoglobin, or duration of diabetes. CONCLUSIONS: Endothelium-dependent vasodilation is abnormal in forearm resistance vessels of patients with insulin-dependent diabetes mellitus. This abnormality may be relevant to the high prevalence of vascular disease that occurs in these individuals.

Contribution of vasopressin to blood pressure regulation during hypovolemic hypotension in humans.

In animals subjected to hemorrhage, plasma arginine vasopressin concentrations increase to levels sufficient to cause vasoconstriction, thus attenuating the hypotensive response. The purpose of this study was to examine the contribution of vasopressin to blood pressure regulation during hypotension in humans. Hypotension was induced in twelve normal subjects by lower body negative pressure (LBNP) before and after intravenous administration of vasopressin V1 receptor antagonist. Before drug administration, LBNP reduced systolic blood pressure from 125 +/- 4 to 78 +/- 12 mmHg (P < 0.01) as vasopressin concentration increased from 2.9 +/- 0.6 to 17 +/- 6 pg/ml (P < 0.05). After administration of the vasopressin antagonist, LBNP reduced systolic blood pressure from 128 +/- 3 to 89 +/- 11 mmHg (P < 0.01). The hypotensive response to LBNP was not potentiated by inhibiting vasopressin's vasoconstrictive effects (P = NS). Thus hypotension causes marked increases in plasma vasopressin concentration. In contrast to findings in animal studies, however, vasopressin does not contribute to the maintenance of blood pressure during hypotension in humans.