Intracerebroventricular losartan infusion modulates angiotensin II type 1 receptor expression in the subfornical organ and drinking behaviour in bile-duct-ligated rats.

Abstract

Bile duct ligation (BDL) causes congestive liver failure that initiates haemodynamic changes, including peripheral vasodilatation and generalized oedema. Peripheral vasodilatation is hypothesized to activate compensatory mechanisms, including increased drinking behaviour and neurohumoral activation. This study tested the hypothesis that changes in the expression of angiotensin II type 1 receptor (AT(1)R) mRNA and protein in the lamina terminalis are associated with BDL-induced hyposmolality in the rat. All rats received either BDL or sham-ligation surgery. The rats were housed in metabolic chambers for measurement of fluid and food intake and urine output. Expression of AT(1)R in the lamina terminalis was assessed by Western blot and quantitative real-time PCR (RT-qPCR). Average baseline water intake increased significantly in BDL rats compared with sham-operated rats, and upregulation of AT(1)R protein and AT(1a)R mRNA were observed in the subfornical organ of BDL rats. Separate groups of BDL and sham-ligated rats were instrumented with minipumps filled with either losartan (2.0 μg μl(-1)) or 0.9% saline for chronic intracerebroventricular or chronic subcutaneous infusion. Chronic intracerebroventricular losartan infusion attenuated the increased drinking behaviour and prevented the increased abundance of AT(1)R protein in the subfornical organ in BDL rats. Chronic subcutaneous infusion did not affect water intake or AT(1)R abundance in the subfornical organ. The data presented here indicate a possible role of increased central AT(1)R expression in the regulation of drinking behaviour during congestive cirrhosis.