Haemodynamic, renal sodium handling, and neurohormonal effects of acute administration of low dose losartan, an angiotensin II receptor antagonist, in preascitic cirrhosis

Background-The renin-angiotensin system may be implicated in the subtle sod ium handling abnormality in. preascitic cirrhosis. Aims-To assess the role of angiotensin II in sodium homoeostasis in preasci tic cirrhosis, using losartan, its preascitic receptor cirrhosis, antagonis t. Patients-Nine male, preascitic cirrhotic patients, and six age matched, hea lthy male controls. Methods-A dose response study using 2.5, 5, 7.5, and 10 mg of losartan was performed on a daily 200 mmol sodium intake, followed by repeat studies wit h the optimal dose, 7.5 mg of losartan, to determine its effects on systemi c and renal haemodynamics, renal sodium handling, and neurohumoral factors. Results-Preascitic cirrhotic patients had significantly reduced baseline ur inary sodium excretion compared with controls (154 (8) versus 191 (12)/mmol /day, p<0.05), associated with significantly reduced systemic angiotensin I I levels (6.0 (1.7) versus 39.5 (10.0) pmol/l, p=0.002). Losartan 7.5 mg no rmalised renal sodium handling in the preascitic cirrhotic patients (202 (1 2) mmol/day, p=0.05 versus baseline), without any change in systemic or ren al haemodynamics, but with. significantly increased systemic angiotensin II levels (7.8 (2.3) pmol/l, p=0.05 versus baseline). Losartan had no effect on renal sodium handling in controls. Conclusions-In preascitic cirrhotic patients, the subtle renal sodium reten tion, paradoxically associated with law systemic neurohumoral factor levels , is improved with low dose losartan, suggesting the involvement of angiote nsin II via its direct action on the renal tubule.