Distinct effects of bosentan on NO-dependent vasodilation and calcium influx in heterozygous Ren-2 transgenic rats on high-salt diet

Title:

Distinct effects of bosentan on NO-dependent vasodilation and calcium influx in heterozygous Ren-2 transgenic rats on high-salt diet

Creator:

Vaněčková, I., Hojná, S., Kadlecová, M., Kompanowska-Jezierska, E., and Zicha, J.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:918b586e-300a-490d-81d7-e6a29dc80d83
uuid:918b586e-300a-490d-81d7-e6a29dc80d83
doi:10.33549/physiolres.934192

Subject:

hypertension, bosentan, vasoactive systems, and blood pressure regulation

Type:

model:article and TEXT

Format:

bez média and svazek

Description:

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-weekold (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 highsalt 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.

Language:

English

Rights:

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

Coverage:

717-725

Source:

Physiological research | 2019 Volume:68 | Number:5

Harvested from:

CDK

Metadata only:

false