Improved endothelial function after endothelin receptor blockade in patients with systemic sclerosis
Cardillo C et al. – Endothelin 1 (ET-1)-dependent vasoconstrictor tone is increased predominantly in the subgroup of systemic sclerosis (SSc) patients with diffuse cutaneous SSc (dcSSc), in whom acute blockade of ETA receptors was able to improve impaired endothelium-dependent vasodilator function, suggesting a novel vasculoprotective effects of ETA receptor antagonism.Methods- An investigation of whether increased activity of ET-1 system plays a role in the occurrence of endothelial dysfunction in pts with SSc
- 12 pts with SSc: 6 with dcSSc, 6 with limited cutaneous SSc (lcSSc)
- Forearm blood flow responses to graded doses of acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed by plethysmography, during infusion of saline and following selective blockade of ETA receptors with BQ-123
Results- During saline infusion, the vasodilator response to ACh was blunted in pts with SSc vs healthy controls
- Whereas response to SNP was not different between groups
- Vasodilator effect of ETA receptor antagonism was higher in pts, indicating enhanced ET-1-mediated vasoconstriction in SSc
- In pts, ETA receptor blockade resulted in a potentiation of the vasodilator response to Ach, but did not affect the response to SNP
- Both the vasodilator effect of ETA receptor antagonism and the improvement in the responsiveness to ACh following BQ-123 infusion were higher in pts with dcSSc vs lcSSc
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