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

• Published in: Gut Vol. 46; no. 1; pp. 114 - 120
• Main Authors: Girgrah, N, Liu, P, Collier, J, Blendis, L, Wong, F
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.01.2000; BMJ; BMJ Publishing Group LTD
• Subjects: Adult; Aged; Alcohol; Angiotensin II - physiology; angiotensin II receptor antagonist; Angiotensin Receptor Antagonists; Ascites - physiopathology; Biological and medical sciences; Digestive system; Dose-Response Relationship, Drug; Hemodynamics - drug effects; Homeostasis - drug effects; Humans; Kidney - metabolism; Liver cirrhosis; Liver Cirrhosis - physiopathology; Losartan - administration & dosage; Losartan - pharmacology; Male; Medical sciences; Middle Aged; Nutrition research; Patients; Pharmacology. Drug treatments; preascitic cirrhosis; renal haemodynamics; renin-angiotensin-aldosterone system; Retention; Rodents; Sodium; Sodium - urine; sodium retention; Urinalysis; Urine; Kidney disease; Human; Urinary system disease; Renal function; Peptides; Pathophysiology; Low dose; Cardiovascular disease; Hepatic disease; Retention; Result; Cirrhosis; Chemotherapy; Sodium; Digestive diseases; Vasoconstrictor agent; Complication; Hemodynamics; Angiotensin II; Ascites; Pharmacokinetics
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.46.1.114

BACKGROUND The renin-angiotensin system may be implicated in the subtle sodium handling abnormality in preascitic cirrhosis. AIMS To assess the role of angiotensin II in sodium homoeostasis in preascitic cirrhosis, using losartan, its receptor antagonist. PATIENTS Nine male, preascitic cirrhotic patients, and six age matched, healthy 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 with the optimal dose, 7.5 mg of losartan, to determine its effects on systemic and renal haemodynamics, renal sodium handling, and neurohumoral factors. RESULTS Preascitic cirrhotic patients had significantly reduced baseline urinary sodium excretion compared with controls (154 (8) versus 191 (12) mmol/day, p<0.05), associated with significantly reduced systemic angiotensin II levels (6.0 (1.7) versus 39.5 (10.0) pmol/l, p=0.002). Losartan 7.5 mg normalised renal sodium handling in the preascitic cirrhotic patients (202 (12) mmol/day, p=0.05 versus baseline), without any change in systemic or renal 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 retention, paradoxically associated with low systemic neurohumoral factor levels, is improved with low dose losartan, suggesting the involvement of angiotensin II via its direct action on the renal tubule.