Effect of losartan on sodium appetite of hypothyroid rats subjected to water and sodium depletion and water, sodium and food deprivation

The involvement of angiotensin AT1 receptors in sodium appetite was studied in hypothyroid rats treated with the angiotensin II antagonist losartan. L osartan was administered chronically by the oral route or acutely by the su bcutaneous route after water and sodium depletion or water, sodium and food deprivation. Three days after addition of losartan to the food at the dose of 1.0 mg g(-1), the rats significantly reduced (P < 0.02) their spontaneo us intake of 1.8% NaCl. Increasing the dose of losartan to 2.0 and 4.0 mg g (-1) did not reduce NaCl intake; in contrast, the intensity of the sodium a ppetite gradually returned to previous levels. The simultaneous administrat ion of captopril, an angiotensin converting enzyme inhibitor, and losartan significantly increased (P < 0.05) NaCl intake and after captopril removal NaCl intake returned to the levels observed with losartan treatment alone. The administration of losartan 4 days after the beginning of captopril trea tment significantly reduced (P < 0.0001) NaCl intake. Following acute admin istration of losartan, water- and sodium-depleted rats significantly reduce d their NaCl and water intake (P < 0.001). The administration of losartan a lso induced a significant reduction in NaCl and water intake in water, NaCl and food-deprived rats (P < 0.0001 and P < 0.001, respectively). The prese nt results show that chronic treatment with oral losartan inhibited spontan eous sodium appetite in hypothyroid rats. Continuation of treatment rendere d rats resistant to the blockade of AT1 receptors. Water and sodium depleti on and water, NaCl and food deprivation induced sodium appetite, which in t he short term depends on cerebral angiotensinergic activity mediated by the activation of AT1 receptors.