Distinct Effects of Bosentan on NO-Dependent Vasodilation and Calcium Influx in Heterozygous Ren-2 Transgenic Rats on High-Salt Diet

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00511973" target="_blank" >RIV/67985823:_____/19:00511973 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.biomed.cas.cz/physiolres/pdf/2019/68_717.pdf" target="_blank" >http://www.biomed.cas.cz/physiolres/pdf/2019/68_717.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.33549/physiolres.934192" target="_blank" >10.33549/physiolres.934192</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Distinct Effects of Bosentan on NO-Dependent Vasodilation and Calcium Influx in Heterozygous Ren-2 Transgenic Rats on High-Salt Diet

Popis výsledku v původním jazyce

Our studies in hypertensive Ren-2 transgenic rats (TGR) demonstrated that chronic administration of atrasentan (ETA receptor antagonist) decreased blood pressure by reduced Ca2+ influx through L-type voltage-dependent calcium channels (L-VDCC) and attenuated angiotensin II-dependent vasoconstriction. We were interested whether bosentan (nonselective ETA/ETB receptor antagonist) would have similar effects. Young 4-week-old (preventive study) and adult 8-week-old (therapeutic study) heterozygous TGR and their normotensive Hannover Sprague-Dawley (HanSD) controls were fed normal-salt (NS, 0.6 % NaCl) or high-salt (HS, 2 % NaCl) diet for 8 weeks. An additional group of TGR fed HS was treated with bosentan (100 mg/kg/day). Bosentan had no effect on BP of TGR fed high-salt diet in both the preventive and therapeutic studies. There was no difference in the contribution of angiotensin II-dependent and sympathetic vasoconstriction in bosentan-treated TGR compared to untreated TGR under the condition of high-salt intake. However, bosentan significantly reduced NO-dependent vasodilation and nifedipine-sensitive BP component in TGR on HS diet. A highly important correlation of nifedipine-induced BP change and the BP after L-NAME administration was demonstrated. Although bosentan did not result in any blood pressure lowering effects, it substantially influenced NO-dependent vasodilation and calcium influx through L-VDCC in the heterozygous TGR fed HS diet. A significant correlation of nifedipine-induced BP change and the BP after L-NAME administration suggests an important role of nitric oxide in the closure of L-type voltage dependent calcium channels.

Název v anglickém jazyce

Distinct Effects of Bosentan on NO-Dependent Vasodilation and Calcium Influx in Heterozygous Ren-2 Transgenic Rats on High-Salt Diet

Popis výsledku anglicky

Our studies in hypertensive Ren-2 transgenic rats (TGR) demonstrated that chronic administration of atrasentan (ETA receptor antagonist) decreased blood pressure by reduced Ca2+ influx through L-type voltage-dependent calcium channels (L-VDCC) and attenuated angiotensin II-dependent vasoconstriction. We were interested whether bosentan (nonselective ETA/ETB receptor antagonist) would have similar effects. Young 4-week-old (preventive study) and adult 8-week-old (therapeutic study) heterozygous TGR and their normotensive Hannover Sprague-Dawley (HanSD) controls were fed normal-salt (NS, 0.6 % NaCl) or high-salt (HS, 2 % NaCl) diet for 8 weeks. An additional group of TGR fed HS was treated with bosentan (100 mg/kg/day). Bosentan had no effect on BP of TGR fed high-salt diet in both the preventive and therapeutic studies. There was no difference in the contribution of angiotensin II-dependent and sympathetic vasoconstriction in bosentan-treated TGR compared to untreated TGR under the condition of high-salt intake. However, bosentan significantly reduced NO-dependent vasodilation and nifedipine-sensitive BP component in TGR on HS diet. A highly important correlation of nifedipine-induced BP change and the BP after L-NAME administration was demonstrated. Although bosentan did not result in any blood pressure lowering effects, it substantially influenced NO-dependent vasodilation and calcium influx through L-VDCC in the heterozygous TGR fed HS diet. A significant correlation of nifedipine-induced BP change and the BP after L-NAME administration suggests an important role of nitric oxide in the closure of L-type voltage dependent calcium channels.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

<a href="/cs/project/NV15-25396A" target="_blank" >NV15-25396A: Centrální a periferní modulace cévního tonu a vylučování sodíku: úloha mozku a ledvin v patofyziologii hypertenze</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

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

5

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

9

Strana od-do

717-725

Kód UT WoS článku

000493949900003

EID výsledku v databázi Scopus

2-s2.0-85074676040