Improved Endothelial Function After Endothelin Receptor Blockade in Patients With Systemic Sclerosis

被引:11
作者
Cardillo, Carmine [1 ]
Schinzari, Francesca
Melina, Domenico
Mores, Nadia
Bosello, Silvia
Peluso, Giusy
Zoli, Angelo
Ferraccioli, Gianfranco
机构
[1] Univ Cattolica Sacro Cuore, Ist Patol Speciale Med & Semeiot Med, I-00168 Rome, Italy
来源
ARTHRITIS AND RHEUMATISM | 2009年 / 60卷 / 06期
关键词
DEPENDENT VASODILATION; BOSENTAN; SCLERODERMA; INHIBITION; DISEASE;
D O I
10.1002/art.24502
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. Impaired endothelium-dependent vasodilator function may contribute to vascular damage in patients with systemic sclerosis (SSc). This study was undertaken to investigate whether increased activity of the endothelin 1 (ET-1) system plays a role in the occurrence of endothelial dysfunction in patients with SSc. Methods. In 12 patients with SSc (6 with diffuse cutaneous SSc [dcSSc) and 6 with limited cutaneous SSc [IcSSc]), forearm blood flow responses to graded doses of acetylcholine (ACh) and sodium nitroprusside (SNP) given intraarterially were assessed by plethysmography, during infusion of saline and following selective blockade of ETA receptors with BQ-123 (10 nmoles/minute). Results. During saline infusion, the vasodilator response to ACh was blunted in patients with SSc as compared with that in healthy controls (P < 0.001), whereas the response to SNP was not different between groups (P = 0.27). The vasodilator effect of ETA receptor antagonism was higher in patients than in controls (P < 0.001), indicating enhanced ET-1-mediated vasoconstriction in SSc. In patients, ETA receptor blockade resulted in a potentiation of the vasodilator response to ACh (P < 0.001 versus saline), but did not affect the response to SNP (P = 0.31). Notably, both the vasodilator effect of ETA receptor antagonism and the improvement in the responsiveness to ACh following BQ-123 infusion were higher in patients with dcSSc than in those with IcSSc (P < 0.01). Conclusion. ET-1-dependent vasoconstrictor tone is increased predominantly in the subgroup of SSc patients with dcSSc, in whom acute blockade of ETA receptors was able to improve impaired endothelium-dependent vasodilator function. Our results suggest novel vasculoprotective effects of ETA receptor antagonism and support further exploration of strategies that target the ET-1 pathway in SSc.
引用
收藏
页码:1840 / 1844
页数:5
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