Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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 (ET(A)) 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-N(G)-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 ET(A) receptor-mediated vascular tone. However, despite otherwise normal vascular function, there was reduced responsiveness to exogenous endothelin-1, possibly reflecting overactivity of this system and ET(A) receptor downregulation.

Original publication




Journal article


J am coll cardiol

Publication Date





1585 - 1590


Analysis of Variance, Endothelin Receptor Antagonists, Endothelin-1, Enzyme Inhibitors, Female, Humans, Male, Microvascular Angina, Middle Aged, Nitric Oxide, Nitroprusside, Peptides, Cyclic, Regression Analysis, Vascular Resistance, Vasodilator Agents, omega-N-Methylarginine