Anti-inflammatory effects of endothelin receptor blockade in left atrial tissue of spontaneously hypertensive rats

• DOI: 10.1016/j.ijcha.2022.101088
• Publication Date: 2022-07-20T22:09:23Z
• Authors: A. Bukowska; Y. Nikonova; C. Wolke; U. Lendeckel; J. Kockskämper; A. Goette
• Keywords: Doxazosin

In spontaneously hypertensive rats (SHR) atrial remodeling has been shown to involve increase in endothelin (ET) signaling. Furthermore, inflammatory processes may further contribute tissue remodeling. The aimed of this study was investigate whether an receptor antagonist, macitentan, could reduce left (LA) arterial hypertension.Molecular characterization atria performed SHR at the age 8 months and their age-matched normotensive control (WKY). were treated with macitentan and, for comparison a blood pressure reducing drug, doxazosin. After two treatment, molecules involved endocardial inflammation calcium handling assessed. molecular changes provoked by rapid-pacing (RAP) analyzed slices.Doxazosin reduced systolic compared untreated (159 ± 26 vs. 176 17; P < 0.05) or (vs. 189 21; 0.05). Macitentan lowered increased levels ET-1 abrogated pacing-induced upregulation preproET-1-mRNA slices from SHR. elevated 8-isoprostanes, expression pro-inflammatory ICAM-1 IL-8, phosphorylation MAP kinases, ERK p38, NF-κB VCAM-mRNA. Major Ca2+-regulating proteins markers hypertrophy fibrosis, however, not affected. Doxazosin elicited similar changes, except alterations levels, VCAM-mRNA.Macitentan reversed pressure-independent manner, which might prevent dysfunction thereby, thrombogenesis hypertension.