AT 1 receptor blockade with losartan during gestation in Wistar rats leads to an increase in thirst and sodium appetite in their adult female offspring

Abstract

We studied the effects of angiotensin II receptor blockade with losartan on thirst and sodium appetite in pregnant Wistar rats and on their adult female offspring. During maternal adaptation to pregnancy, average daily total water intake increased by 63% ( P<0.01); NaCl intake by 214% ( P<0.001). These changes were not blocked by daily s.c. injections of losartan (50 mg/kg bw i.p.) from gestation day (GD) 2 until GD 19 which implied that maternal AT 1 receptors were not involved in the up regulation of thirst and sodium appetite during pregnancy. Losartan blockade during gestation led to a significant and continued increase in thirst and sodium appetite in the adult female offspring. Daily water intakes were greater in the losartan (LO) group than in the vehicle-injected control group (CO), leading to a total water intake of 1114±80.6 ml/kg bw compared with 738±56.7 ml/kg bw ( P<0.05) during the 8-day period of observation. Daily sodium intakes were usually 2–3 times greater in the LO group compared with the CO group, amounting to a final cumulative intake of 232±33 mmol/kg bw compared with 93.8±16.5 mmol/kg bw ( P<0.05) in 8 days. These elevated sodium and water intakes were nearly counterbalanced by the increased renal excretion of water and sodium by fully functional kidneys that were not injured by the drug. Body weights were 10% lower in the LO group at the start but remained unchanged relative to the CO group during the entire 8-day period of observation. Plasma electrolytes, blood hematocrit and carotid MABP in the LO group did not differ from the CO group.