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

Title:

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

Creator:

Kala, P. , Červenka, L., Škaroupková, P. , Táborský, M. , Kompanowska-Jezierska, E. , and Sadowski, J.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:3d38ef21-b078-43c0-a31b-4d94759c56d9
uuid:3d38ef21-b078-43c0-a31b-4d94759c56d9
doi:10.33549/physiolres.934094

Type:

model:article and TEXT

Format:

bez média and svazek

Description:

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.

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Coverage:

589-601

Source:

Physiological research | 2019 Volume:68 | Number:4

Harvested from:

CDK

Metadata only:

false