The treatment with sGC stimulator improves survival of hypertensive rats in response to volume-overload induced by aorto-caval fistula

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F23%3A00083992" target="_blank" >RIV/00023001:_____/23:00083992 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/23:73619274 RIV/00098892:_____/23:10158026

Výsledek na webu

<a href="https://link.springer.com/article/10.1007/s00210-023-02561-y" target="_blank" >https://link.springer.com/article/10.1007/s00210-023-02561-y</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00210-023-02561-y" target="_blank" >10.1007/s00210-023-02561-y</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The treatment with sGC stimulator improves survival of hypertensive rats in response to volume-overload induced by aorto-caval fistula

Popis výsledku v původním jazyce

Heart failure (HF) has been declared as global pandemic and current therapies are still ineffective, especially in patients that develop concurrent cardio-renal syndrome. Considerable attention has been focused on the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway. In the current study, we aimed to investigate the effectiveness of sGC stimulator (BAY41-8543) with the same mode of action as vericiguat, for the treatment of heart failure (HF) with cardio-renal syndrome. As a model, we chose heterozygous Ren-2 transgenic rats (TGR), with high-output heart failure, induced by aorto-caval fistula (ACF). The rats were subjected into three experimental protocols to evaluate short-term effects of the treatment, impact on blood pressure, and finally the long-term survival lasting 210 days. As control groups, we used hypertensive sham TGR and normotensive sham HanSD rats. We have shown that the sGC stimulator effectively increased the survival of rats with HF in comparison to untreated animals. After 60 days of sGC stimulator treatment, the survival was still 50% compared to 8% in the untreated rats. One-week treatment with sGC stimulator increased the excretion of cGMP in ACF TGR (109 +/- 28 nnmol/12 h), but the ACE inhibitor decreased it (-63 +/- 21 nnmol/12 h). Moreover, sGC stimulator caused a decrease in SBP, but this effect was only temporary (day 0: 117 +/- 3; day 2: 108 +/- 1; day 14: 124 +/- 2 mmHg). These results support the concept that sGC stimulators might represent a valuable class of drugs to battle heart failure especially with cardio-renal syndrome, but further studies are necessary.

Název v anglickém jazyce

The treatment with sGC stimulator improves survival of hypertensive rats in response to volume-overload induced by aorto-caval fistula

Popis výsledku anglicky

Heart failure (HF) has been declared as global pandemic and current therapies are still ineffective, especially in patients that develop concurrent cardio-renal syndrome. Considerable attention has been focused on the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway. In the current study, we aimed to investigate the effectiveness of sGC stimulator (BAY41-8543) with the same mode of action as vericiguat, for the treatment of heart failure (HF) with cardio-renal syndrome. As a model, we chose heterozygous Ren-2 transgenic rats (TGR), with high-output heart failure, induced by aorto-caval fistula (ACF). The rats were subjected into three experimental protocols to evaluate short-term effects of the treatment, impact on blood pressure, and finally the long-term survival lasting 210 days. As control groups, we used hypertensive sham TGR and normotensive sham HanSD rats. We have shown that the sGC stimulator effectively increased the survival of rats with HF in comparison to untreated animals. After 60 days of sGC stimulator treatment, the survival was still 50% compared to 8% in the untreated rats. One-week treatment with sGC stimulator increased the excretion of cGMP in ACF TGR (109 +/- 28 nnmol/12 h), but the ACE inhibitor decreased it (-63 +/- 21 nnmol/12 h). Moreover, sGC stimulator caused a decrease in SBP, but this effect was only temporary (day 0: 117 +/- 3; day 2: 108 +/- 1; day 14: 124 +/- 2 mmHg). These results support the concept that sGC stimulators might represent a valuable class of drugs to battle heart failure especially with cardio-renal syndrome, but further studies are necessary.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Naunyn-Schmiedeberg&apos;s archives of pharmacology

ISSN

0028-1298

e-ISSN

1432-1912

Svazek periodika

396

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

3757-3773

Kód UT WoS článku

001015575600006

EID výsledku v databázi Scopus

2-s2.0-85162252872