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

0511973 - FGÚ 2020 RIV CZ eng J - Journal Article
Vaněčková, Ivana - Hojná, Silvie - Kadlecová, Michaela - Kompanowska - Jezierska, E. - Zicha, Josef
Distinct Effects of Bosentan on NO-Dependent Vasodilation and Calcium Influx in Heterozygous Ren-2 Transgenic Rats on High-Salt Diet.
Physiological Research. Roč. 68, č. 5 (2019), s. 717-725. ISSN 0862-8408. E-ISSN 1802-9973
R&D Projects: GA MZd(CZ) NV15-25396A
Grant - others:AV ČR(CZ) PAN-17-13
Program: Bilaterální spolupráce
Institutional support: RVO:67985823
Keywords : hypertension * bosentan * vasoactive systems * blood pressure regulation
OECD category: Cardiac and Cardiovascular systems
Impact factor: 1.655, year: 2019
Method of publishing: Open access
http://www.biomed.cas.cz/physiolres/pdf/2019/68_717.pdf

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.
Permanent Link: http://hdl.handle.net/11104/0302206