首页   按字顺浏览 期刊浏览 卷期浏览 Functional characterization of endothelin receptors in hypertensive resistance vessels
Functional characterization of endothelin receptors in hypertensive resistance vessels

 

作者: Monica Montagnani,   Maria Potenza,   Rosanna Rinaldi,   Gianfranco Mansi,   Carmela Nacci,   Miralma Serio,   Vito Vulpis,   Anna Pirrelli,   Delia Mitolo-Chieppa,  

 

期刊: Journal of Hypertension  (OVID Available online 1999)
卷期: Volume 17, issue 1  

页码: 45-52

 

ISSN:0263-6352

 

年代: 1999

 

出版商: OVID

 

关键词: endothelin-1;rat mesenteric vascular bed;receptor responsiveness;spontaneously hypertensive rats

 

数据来源: OVID

 

摘要:

ObjectiveThe physiological and pathophysiological functions of endothelin-1 in modulating the regional blood flow of normal and spontaneously hypertensive rats (SHR) were studied in the perfused mesenteric vascular bed, a useful model for investigating resistance vessels.Design and methodsWe used 12-week-old SHR and Wistar–Kyoto (WKY) rats. Endothelin A (ETA) receptor responsiveness was evaluated by endothelin-1 (0.2–2 μmol/l) concentration–response curves, and repeated in the presence of indomethacin and the ETAand endothelin B (ETB) receptor antagonists BQ-485 and BQ-788, respectively. ETBreceptor responsiveness was tested by sarafotoxin S6c concentration–response curves, obtained in the noradrenaline-precontracted mesenteric vascular bed, and repeated after treatment with BQ-788 and after endothelial denudation.ResultsIn both groups, endothelin-1 induced concentration-dependent contraction; SHR exhibited a markedly increased maximal effect compared with WKY rats (P< 0.01). BQ-485 produced a shift to the right for endothelin-1 concentration–response curves in both groups, with a higher pA2(negative common logarithm of the antagonist that produces an agonist dose ratio of 2) value in SHR than in WKY rats (P< 0.01). The increase in the maximal effect produced by endothelin-1 in SHR was prevented by indomethacin, which also induced a significant increase in the endothelin-1 concentration producing the half-maximal response (EC50) in SHR (P< 0.05). Sarafotoxin S6c produced an ETB-dependent endothelium-mediated relaxant effect in WKY rats, which was not observed in SHR.ConclusionsThe higher vasoconstriction induced by endothelin-1 in SHR may be related to a greater number of available ETAreceptors, due to the presence of an ETAreceptor subtype. This mechanism may be linked to the production of prostanoids that add to the direct endothelin-1-evoked vasoconstriction. These results, together with the lack of relaxation in response to sarafotoxin S6c in SHR, suggest that an imbalance in the endothelin-1 ability to induce both contraction and relaxation is present in SHR with sustained hypertension, manifesting as a greater contractile effect evoked in this strain.

 

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