Reduced responsiveness to endothelin-1 in peripheral resistance vessels of patients with syndrome X

David E Newby, Laura Flint, Keith A A Fox, Nicholas A. Boon, David J Webb

Research output: Contribution to journalArticlepeer-review


This study sought to assess the contribution and action of nitric oxide and endothelin-1 in peripheral resistance vessels of patients with syndrome X.
Patients with syndrome X may have a generalized disorder of vascular and endothelial function, promoting vasospasm.
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.
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).
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 languageEnglish
Pages (from-to)1585-90
Number of pages6
JournalJournal of the American College of Cardiology
Issue number7
Publication statusPublished - 21 May 1999


  • 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


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