effect of losartan on the kidney of adult female albino mice and on the renal, hepatic and pulmonary tissues of their fetuses

ABSTRACT

Angiotensin receptor blockers as well as angiotensin-converting enzyme inhibitors are antihypertensive medications prescribed by a wide variety of physicians. Blocking of angiotensin II [ANG II] mainly through angiotensin II type I receptor [AT[1]] has been implicated in mediating the angiotensin-converting enzyme [ACE] inhibition. The present study was designed to investigate the effects of an AT[1] antagonist, losartan, on the renal tissues of adult and fetus as well as the hepatic and pulmonary tissues of fetuses histologically and ultrastructurally. Pregnant CD-1 mice were used in this study and they were administered losartan orally through gastric tube. Animals were divided into three groups; the first group served as control, while the second and third groups were administered losartan [10 mg/kg/day] during the second and third weeks of pregnancy respectively. At the end of pregnancy, the pregnant females were sacrificed and the fetuses were removed where the kidney of both adult and fetuses as well as the liver and lung of fetuses were removed. Light and electron microscopic examination of the selected tissues revealed conspicuous pathological lesions especially in the second group. Renal lesions were represented by hypertrophied glomeruli with a marked increase in mesangial cells, interstitial fibroblasts proliferation and haemorrhage. Ultrastructural changes were represented by thickening of the glomerular basement membrane, fusion of foot processes and tubular necrosis in both adult and fetuses. Moreover, the fetal liver of the second group showed marked accumulation of glycogen contents, fatty degeneration, necrosis and nuclear pyknosis. The fetal lung revealed remarkable damage of the epithelial cells lining the respiratory bronchioles, focal areas of cellular necrosis, moderate increase in pneumocytes type II and macrophages. A marked increase in number of alveolar fibroblasts was also observed. Consequently, such pathological lesions induced by losartan-treatment might lead to renal dysfunction, hepatic injury and chronic lung inflammation. Thus, extreme caution seems to be necessary in losartan treatment during pregnancy. It is essential to balance the risks of toxicity from drug treatment, the hazards of the fetus against the risks of non treatment during the second trimester of pregnancy