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Improved endothelial function after endothelin receptor blockade in patients with systemic sclerosis.
Arthritis Rheum. 2009 Jun; 60(6):1840-4.AR

Abstract

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 [lcSSc]), 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 lcSSc (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.

Authors+Show Affiliations

Istituto di Patologia Speciale Medica e Semeiotica Medica, Università Cattolica del Sacro Cuore, and Association Columbus, Rome, Italy. carmine.cardillo@rm.unicatt.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19479828

Citation

Cardillo, Carmine, et al. "Improved Endothelial Function After Endothelin Receptor Blockade in Patients With Systemic Sclerosis." Arthritis and Rheumatism, vol. 60, no. 6, 2009, pp. 1840-4.
Cardillo C, Schinzari F, Melina D, et al. Improved endothelial function after endothelin receptor blockade in patients with systemic sclerosis. Arthritis Rheum. 2009;60(6):1840-4.
Cardillo, C., Schinzari, F., Melina, D., Mores, N., Bosello, S., Peluso, G., Zoli, A., & Ferraccioli, G. (2009). Improved endothelial function after endothelin receptor blockade in patients with systemic sclerosis. Arthritis and Rheumatism, 60(6), 1840-4. https://doi.org/10.1002/art.24502
Cardillo C, et al. Improved Endothelial Function After Endothelin Receptor Blockade in Patients With Systemic Sclerosis. Arthritis Rheum. 2009;60(6):1840-4. PubMed PMID: 19479828.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improved endothelial function after endothelin receptor blockade in patients with systemic sclerosis. AU - Cardillo,Carmine, AU - Schinzari,Francesca, AU - Melina,Domenico, AU - Mores,Nadia, AU - Bosello,Silvia, AU - Peluso,Giusy, AU - Zoli,Angelo, AU - Ferraccioli,Gianfranco, PY - 2009/5/30/entrez PY - 2009/5/30/pubmed PY - 2009/8/18/medline SP - 1840 EP - 4 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 60 IS - 6 N2 - 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 [lcSSc]), 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 lcSSc (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. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/19479828/Improved_endothelial_function_after_endothelin_receptor_blockade_in_patients_with_systemic_sclerosis_ L2 - https://doi.org/10.1002/art.24502 DB - PRIME DP - Unbound Medicine ER -