Moderate additive effects of endothelin receptor A blockade in Ren-2 transgenic rats subjected to various types of RAS blockade

0461894 - FGÚ 2017 RIV GB eng J - Journal Article
Vaněčková, Ivana - Řezáčová, Lenka - Kuneš, Jaroslav - Zicha, Josef
Moderate additive effects of endothelin receptor A blockade in Ren-2 transgenic rats subjected to various types of RAS blockade.
Life Sciences. Roč. 159, Aug 15 (2016), s. 127-154. ISSN 0024-3205. E-ISSN 1879-0631
R&D Projects: GA MZd(CZ) NV15-25396A
Institutional support: RVO:67985823
Keywords : aliskiren * captopril * atrasentan * hypertension * losartan * ren-2 transgenic rats
Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery
Impact factor: 2.936, year: 2016

We tested whether the addition of ETA blockade to renin-angiotensin system (RAS) blockade would have further effects on the principal vasoactive systems contributing to BP maintenance in Ren-2 transgenic rats (TGR). We found that all RAS blockers similarly decreased BP to normotension, their effects being mediated through substantially attenuated RAS-dependent and moderately decreased SNS-dependent vasoconstriction. Atrasentan alone partially lowered BP, while BP was normalized by combination of atrasentan with either RAS blocker. In combination therapies, BP lowering effects resulted from the attenuation of both RAS- and SNS-dependent vasoconstriction. Moreover, atrasentan-treated groups had substantially reduced NO-dependent vasodilation and significantly decreased calcium influx through L-VDCC. In conclusion, Although the BP-lowering effect of combined ETA and RAS blockades in TGR is predominantly dependent on the effects exerted by RAS blockade, further effects are attributable to decreased calcium influx due to chronic ETA blockade.
Permanent Link: http://hdl.handle.net/11104/0261451