Angiotensin converting enzyme inhibition decreases cell turnover in the neonatal XXXX heart.

@entity8 @entity851 @entity4688 @entity296 @entity1976 @entity35 @entity1184 @entity2514 @entity3449 @entity1975 @entity299 @entity1811 @entity551 @entity5613
The @entity3449 angiotensin system plays an important role in growth and development. Exposure of the neonate to an @entity1811 inhibitor increases mortality and results in @entity851 and abnormal development. We have demonstrated that @entity1811 inhibition in the developing kidney increases apoptosis and decreases cell proliferation, which may account for @entity8 . To evaluate the role of endogenous angiotensin in cardiac development, the relationship between @entity1811 inhibition, cell proliferation, apoptosis, several modulators of apoptosis ( @entity1976 , @entity5613 , and clusterin) was examined in the developing @entity35 heart. Thirty-five newborn @entity35 pups were treated with @entity4688 (30 mg/kg/d) or a vehicle (control group) for 7 d, and hearts were removed for rt-PCR and Western blotting of @entity1976 , @entity5613 , and clusterin. An additional 10 @entity35 pups were treated with @entity2514 (10 mg/kg/d) or a vehicle, to serve as a @entity551 control. Cell proliferation was determined by @entity1975 immunostaining, and apoptosis was detected using the total TUNEL technique. @entity4688 treatment resulted in a 24% mortality, reduced body weight, and decreased heart weight (p < 0.05). @entity4688 decreased proliferating myocytes by 23%, and reduced proliferating cardiac interstitial cells by 8.1% (p < 0.05). @entity4688 also decreased myocytes apoptosis by 60%, but the proportion of myocytes undergoing apoptosis was 10-fold less than that of proliferating cells. Cardiac @entity1976 mRNA, clusterin mRNA, @entity1976 protein, and @entity5613 protein content were not changed, but clusterin protein expression was decreased by @entity4688 treatment. @entity2514 did not alter cardiac cell proliferation or apoptosis. We conclude that @entity1811 inhibition decreases cell turnover in the developing @entity35 heart, which may contribute to @entity299 . The loss of myocytes may lead to greater myocyte @entity1184 and @entity296 during later life.
