Effect of endothelin blockade on early cardiovascular remodeling in the one-clip-two-kidney XXXX of the @entity35 .

@entity296 @entity101 @entity35 @entity177 @entity4346 @entity1811 @entity32593
BACKGROUND: In models of @entity101 and of @entity177 , pharmacological blockade of the ET(A) receptor has been shown to cause some inconsistent lowering of blood pressure (BP) and lesser @entity4346 ( @entity4346 ). The effects of ET(A) receptor blockade (ET(A)-RB) on vascular remodeling and their potential relation to BP lowering, have not been clarified. DESIGN: The experimental study in male @entity35 was designed to compare four experimental groups: (1) sham-operated controls (sham); (2) untreated @entity35 with one-clip-two-kidney (1C-2K) renovascular @entity101 ; (3) 1C-2K @entity35 treated with the @entity1811 inhibitor ( @entity1811 -i) trandolapril (0.3 mg/kg b.w./day), and (4) 1C-2K @entity35 treated with the ET(A)-RB @entity32593 (50 mg/kg b.w./day). BP was measured weekly by tail plethysmography. After 3 weeks, animals were sacrificed and cardiac, aortic and mesenteric artery morphology was evaluated using morphometric and stereological techniques. RESULTS: Systolic BP was significantly higher in 1C-2K @entity35 compared to sham. BP was not significantly affected by ET(A)-RB, but was significantly lowered by the @entity1811 -i. Despite no significant change in BP, ET(A)-RB treatment led to a significantly less volume density of the cardiac interstitium (sham 1.40 +/- 0.18, 1C-2K 2.66 +/- 0.56, 1C-2K + @entity1811 -i 1.88 +/- 0.38, 1C-2K + ET(A)-RB 2.15 +/- 0.37%). In contrast, ET(A)-RB had no significant effect on left ventricular/body weight ratio (sham 2.85 +/- 0.26, 1C-2K 2.96 +/- 0.33, 1C-2K + @entity1811 -i 2.54 +/- 0.22 and 1C-2K + ET(A)-RB 3.15 +/- 0.44 mg/g) or on wall thickness of intramyocardial arteries. CONCLUSIONS: The ET(A)-RB @entity32593 ameliorated the development of @entity296 in a short-term hyperreninemic normal salt model of experimental @entity101 nearly as effectively as an @entity1811 -i. This effect of @entity32593 is independent of systemic BP. In contrast to findings in other models, ET(A) receptor blockade had no significant effect on @entity4346 . Only the @entity1811 -i but not the ET(A)-RB prevented structural changes of small intramyocardial arteries and of the aorta.
