Sex-linked differences in the mortality in Ren-2 transgenic hypertensive rats with aorto-caval fistula : effects of treatment with angiotensin converting enzyme alone and combined with inhibitor of soluble epoxide hydrolase.

Autor: Kala, Petr, 1965-
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Jazyk: angličtina
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Druh dokumentu: Non-fiction
ISSN: 0862-8408
Abstrakt: Abstract: We found recently that in Ren-2 transgenic hypertensive rats (TGR) addition of soluble epoxide hydrolase inhibitor (sEHi) to treatment with angiotensin-converting enzyme inhibitor (ACEi), surprisingly, increased the mortality due to heart failure (HF) induced by creation of the aorto-caval fistula (ACF). Since TGR exhibit sex-related differences in mortality, we examined here if such differentiation exists also in the response to the treatment with ACEi (trandolapril), alone or combined with sEHi [cis -4-[4- (3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid, (c -AUCB)]. ACEi improved survival in males to 74 % (vs. 0 %) and in females to 65 % (vs. 32 %). ACEi and sEHi combined also improved the survival in male ACF TGR, however, it was significantly less (38 %) than after ACEi alone. In contrast, in females the combined treatment significantly improved the final survival rate (84 %). There were no significant sex-linked differences in survival rate in untreated or treated normotensive Hannover Sprague-Dawley rats. In conclusion, in HF patients with co-existing hypertension and RAS hyperactivity, the sex may co-determine the rate of HF progression, and can influence the effectiveness of the therapeutic measures applied. Therefore, in the relevant pre-clinical studies the sex-linked differences should be seriously considered. Our data indicate that TGR might be an optimal model for such studies.
Databáze: Katalog Knihovny AV ČR
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