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


CONCLUSIONS
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.
Orth
Stephan R
SR
Department of Internal Medicine II, University of Regensburg, Regensburg, Germany. stephan.orth@gmx.net
Schiele
Günter
G
Banas
Bernhard
B
Ritz
Eberhard
E
Amann
Kerstin
K
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001160:Arterioles / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006984:Hypertrophy; D008297:Male; D009392:Nephrectomy; D010666:Phenylpropionates / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000235:genetics* / Q000503:physiopathology; D017540:Tunica Media / Q000473:pathology; D020257:Ventricular Remodeling / Q000187:drug effects*
D065130:Endothelin A Receptor Antagonists; D010666:Phenylpropionates; D011743:Pyrimidines; C107831:darusentan