Effect of a selective endothelin receptor A blocker on cardiovascular remodeling in uninephrectomized spontaneously hypertensive rats of the stroke-prone strain.

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Orth SR, Schiele G, Banas B, Ritz E, Amann K

Effect of a selective endothelin receptor A blocker on cardiovascular remodeling in uninephrectomized spontaneously hypertensive rats of the stroke-prone strain.

Kidney Blood Press Res. 2007;30(6):400-7. Epub 2007 Sep 20.

PubMed ID

17890870 [ View in PubMed

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Abstract

BACKGROUND/AIMS: The role of endothelin (ET) in cardiovascular remodeling was investigated by treating uninephrectomized spontaneously hypertensive rats of the stroke-prone strain (UNX-SHRsp) on normal- or high (3%)-salt diet with the selective ET(A) receptor blocker LU 135252. METHODS: SHRsp on normal or high salt were sham-operated (n = 10/11) or UNX; UNX received no treatment (n = 10/15) or 100 mg/kg body weight LU 135252 (n = 10/10). Systolic blood pressure (BP) was measured weekly. After perfusion fixation the heart and the aorta were analyzed using quantitative morphological and stereological techniques. RESULTS: No effect was seen in normal-salt groups. In high-salt animals UNX caused left ventricular (LV) hypertrophy which was prevented by LU 135252 (p < 0.001). LU 135252 only lowered BP during the last 2 weeks of the 12-week experiment. UNX showed hypertrophic remodeling of intramyocardial arterioles. Treatment with LU 135252 caused lower wall:lumen ratio and wall thickness of LV intramyocardial arterioles (p < 0.01). In the descending thoracic aorta UNX caused thickening of the media. The media area and the wall:lumen ratio were lower in UNX + LU 135252 as compared to untreated UNX (p < 0.01 and p < 0.05, respectively). CONCLUSION: In SHRsp UNX causes hypertrophic cardiovascular remodeling only in the presence of salt loading. These effects are largely BP-independent and prevented by ET(A) receptor blockade.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Darusentan	Endothelin-1 receptor	Protein	Humans	Unknown	Not Available	Details