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
Jazyk angličtina Země Česko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
31177795
DOI
10.33549/physiolres.934094
PII: 934094
Knihovny.cz E-zdroje
- MeSH
- angiotensin konvertující enzym metabolismus MeSH
- cévní píštěle farmakoterapie genetika mortalita MeSH
- epoxid hydrolasy antagonisté a inhibitory metabolismus MeSH
- hypertenze farmakoterapie genetika mortalita MeSH
- inhibitory ACE aplikace a dávkování MeSH
- inhibitory enzymů aplikace a dávkování MeSH
- kombinovaná farmakoterapie MeSH
- krysa rodu Rattus MeSH
- mortalita trendy MeSH
- náhodné rozdělení MeSH
- pohlavní dimorfismus * MeSH
- potkani Sprague-Dawley MeSH
- potkani transgenní MeSH
- renin * genetika MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- angiotensin konvertující enzym MeSH
- EPHX2 protein, rat MeSH Prohlížeč
- epoxid hydrolasy MeSH
- inhibitory ACE MeSH
- inhibitory enzymů MeSH
- Ren2 protein, rat MeSH Prohlížeč
- renin * MeSH
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.
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