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

Autor: Vaněčková, Ivana, 1964-
Další autoři:
Zicha, Josef, 1950-
Jazyk: angličtina
Předmět:
Druh dokumentu: Non-fiction
ISSN: 0862-8408
Abstrakt: Abstract: 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.
Databáze: Katalog Knihovny AV ČR
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