Artikel
Evidence for Constrictive ET-B Receptors in the Skin Microcirculation of Patients with Atherosclerosis
Hinweis auf konstriktive ET-B Rezeptoren in der Haut-Mikrozirkulation von Patienten mit Arteriosklerose
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Autoren
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A. Mitchell
- Universitätsklinikum Essen (Essen, D)
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U. Rushentsova
- Universitätsklinikum Essen (Essen, D)
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N. Detmer
- Universitätsklinikum Essen (Essen, D)
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T. Philipp
- Universitätsklinikum Essen (Essen, D)
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R. Wenzel
- Allgemeins öffentliches Krankenhaus, Zell am See, Österreich
| Veröffentlicht: | 8. August 2006 |
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Gliederung
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Background: ET-A and ET-B receptors are the main effectors of the endothelin system (ETS) in humans. ET-A and ET-B receptors on smooth muscle cells mediate vasoconstriction, whereas endothelial ET-B receptors mediate vasodilation. Little is known about the role of constrictive ET-B receptors in cardiovascular disease, where the ETS is activated and endothelial function is impaired. We investigated the relative role of ET-A and ET-B receptors for ET-1 mediated vasoconstriction in the skin microcirculation of patients with atherosclerosis.
Study design and methods: 16 patients (PAT; 59.4±2 years) with coronary artery disease or peripheral atherosclerosis were included in a single blind, randomised, placebo controlled cross-over study and were compared to 20 healthy controls (CON; 54.8±2 years). We used a Laser Doppler imager (moor LDI V3.0) to evaluate skin blood flow after injection of ET-1 (10-12, 10-14, 10-16 mol) alone or combined with the ET-A antagonist BQ-123 or the ET-B antagonist BQ-788 (10-8 mol). Data were analyzed with ANOVA and are expressed as changes from baseline in arbitrary perfusion units (PU, mean ± SEM).
Results: ET-1 induced significantly greater vasoconstriction in PAT (PAT -202±90 vs. CON -91±33 PU, P< 0.001). In PAT both BQ788 and BQ123 inhibited ET-1 mediated vasoconstriction (ET-1/BQ788 vs. ET-1: -147±70 vs. -202±90 PU, P= 0.029; ET-1/BQ123 vs. ET-1: -3±23 vs. -202±90 PU, P< 0.0001). In CON BQ123 reduced ET-1 mediated constriction but BQ788 had no effect (ET-1/BQ123 vs. ET-1: -33±14 vs. -91±33 PU, P< 0.0001; ET-1/BQ788 vs. ET-1 -82±35 vs. -91±33 PU, P= 0.50).
Conclusion: We have shown that in atherosclerosis, classically a state of impaired endothelial function, ET-B receptor-mediated vasoconstriction gains importance. Our results will have to be confirmed in other vascular beds but would, preliminarily, suggest that in diseases with endothelial dysfunction patients might profit from combined rather than selective ET-1 receptor antagonism.
