Reduced Responsiveness to Endothelin-1 in Peripheral Resistance Vessels of Patients With Syndrome X

Abstract

Objectives. This study sought to assess the contribution and action of nitric oxide and endothelin-1 in peripheral resistance vessels of patients with syndrome X.Background. Patients with syndrome X may have a generalized disorder of vascular and endothelial function, promoting vasospasm.Methods. Changes in blood flow responses to intrabrachial infusion of the endothelium-dependent vasodilators substance P and acetylcholine, the endothelium-independent nitric oxide donor sodium nitroprusside and the endothelin type A (ETA) receptor antagonist BQ-123 were assessed using venous occlusion plethysmography in 10 patients with syndrome X and 10 matched control subjects. Vasoconstrictor responses to the nitric oxide synthase inhibitor l-NG-monomethyl arginine (l-NMMA) and endothelin-1 were also determined.Results. There were no significant differences in the responses to acetylcholine, substance P, sodium nitroprusside or BQ-123 between patients and control subjects. However, despite similar degrees of vasoconstriction in response to l-NMMA in both groups, endothelin-1 caused a reduction in forearm blood flow of only 20 ± 2% in patients with syndrome X compared with 35 ± 3% in matched control subjects at 90 min (p < 0.001). Although plasma endothelin-1 concentrations were not significantly higher in patients with syndrome X (4.8 vs. 4.0 pg/ml, p = 0.17), the vasoconstriction caused by endothelin-1 infusion correlated inversely with plasma endothelin-1 concentrations (r = −0.51, p = 0.04).Conclusions. Patients with syndrome X had normal basal and stimulated nitric oxide activity and basal endogenous ETAreceptor-mediated vascular tone. However, despite otherwise normal vascular function, there was reduced responsiveness to exogenous endothelin-1, possibly reflecting overactivity of this system and ETAreceptor downregulation.