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

Kód výsledku v IS VaVaI

RIV/00023001:_____/19:00078343 - isvavai.cz

Nalezeny alternativní kódy

RIV/00216208:11130/19:10398476 RIV/00064203:_____/19:10398476

Výsledek na webu

https://www.biomed.cas.cz/physiolres/pdf/2019/68_589.pdf

DOI - Digital Object Identifier

10.33549/physiolres.934094

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

NV17-28220A: Farmakologické zásahy do metabolické cesty cytochromu P-450 jako nový přístup pro léčbu chronického srdečního selhání

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Physiological research

ISSN

0862-8408

e-ISSN

—

Svazek periodika

68

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

13

Strana od-do

589-601

Kód UT WoS článku

000483374200007

EID výsledku v databázi Scopus

2-s2.0-85071711399