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
Language English Country Czech Republic Media print-electronic
Document type Journal Article
PubMed
31177795
DOI
10.33549/physiolres.934094
PII: 934094
Knihovny.cz E-resources
- MeSH
- Peptidyl-Dipeptidase A metabolism MeSH
- Vascular Fistula drug therapy genetics mortality MeSH
- Epoxide Hydrolases antagonists & inhibitors metabolism MeSH
- Hypertension drug therapy genetics mortality MeSH
- Angiotensin-Converting Enzyme Inhibitors administration & dosage MeSH
- Enzyme Inhibitors administration & dosage MeSH
- Drug Therapy, Combination MeSH
- Rats MeSH
- Mortality trends MeSH
- Random Allocation MeSH
- Sex Characteristics * MeSH
- Rats, Sprague-Dawley MeSH
- Rats, Transgenic MeSH
- Renin * genetics MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Peptidyl-Dipeptidase A MeSH
- EPHX2 protein, rat MeSH Browser
- Epoxide Hydrolases MeSH
- Angiotensin-Converting Enzyme Inhibitors MeSH
- Enzyme Inhibitors MeSH
- Ren2 protein, rat MeSH Browser
- 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.
References provided by Crossref.org
Sex-linked differences in the course of thioacetamide-induced acute liver failure in Lewis rats
