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

• Published in: Experimental physiology Vol. 86; no. 5; pp. 621 - 628
• Main Authors: Badauê-Passos, D. Jr, Ventura, R. R., Silva, L. F. S., Olivares, E. L., Ramalho, M. J., Rodrigues, J. Antunes, Reis, L. C.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01-09-2001; The Physiological Society; Blackwell Science Ltd
• Subjects: Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Antihypertensive Agents - pharmacology; Antithyroid Agents - pharmacology; Appetite - drug effects; Diuretics - pharmacology; Drinking; Eating; Food Deprivation - physiology; Full Length Papers; Furosemide - pharmacology; Hypothyroidism - chemically induced; Hypothyroidism - physiopathology; Losartan - pharmacology; Male; Methimazole - pharmacology; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptors, Angiotensin - metabolism; Sodium Chloride - metabolism; Water Deprivation - physiology
• ISSN: 0958-0670; 1469-445X
• DOI: 10.1113/eph8602189

The involvement of angiotensin AT1 receptors in sodium appetite was studied in hypothyroid rats treated with the angiotensin II antagonist losartan. Losartan was administered chronically by the oral route or acutely by the subcutaneous 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 spontaneous 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 appetite gradually returned to previous levels. The simultaneous administration 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 treatment significantly reduced (P < 0.0001) NaCl intake. Following acute administration of losartan, water- and sodium-depleted rats significantly reduced their NaCl and water intake (P < 0.001). The administration of losartan also 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 present results show that chronic treatment with oral losartan inhibited spontaneous sodium appetite in hypothyroid rats. Continuation of treatment rendered rats resistant to the blockade of AT1 receptors. Water and sodium depletion and water, NaCl and food deprivation induced sodium appetite, which in the short term depends on cerebral angiotensinergic activity mediated by the activation of AT1 receptors. Experimental Physiology (2001) 86.5, 621-628.