Role of angiotensin II in regulation of basal and sympathetically stimulated vascular tone in early and advanced cirrhosis

Background & Aims: The renin-angiotensin and sympathetic nervous systems ar e activated in cirrhosis, This study aimed to establish the role of angiote nsin II (ANG II) in the regulation of basal and sympathetically stimulated vascular tone in preascitic cirrhotic patients and patients with diuretic-r efractory ascites compared with age- and sex-matched healthy controls. Meth ods: Forearm blood flow (FBF) responses to lower body negative pressure (LB NP) and to subsystemic, intrabrachial:infusions of losartan, an angiotensin II type 1 (AT(1)) receptor antagonist, norepinephrine, and ANG II were mea sured using venous occlusion plethysmography, Results: In all groups, ANG I I and norepinephrine caused dose-dependent reductions in FBF (P < 0.001); r esponses to norepinephrine were similar across the 3 groups but those to AN G II were less in both cirrhotic groups than in controls (P < 0.01). Losart an caused a dose-dependent increase in FBF only in patients with refractory ascites (P < 0.01), LBNP caused less reduction in FBF in refractory ascite s patients than in both preascitic patients and controls (P < 0.01). Conclu sions: Despite hyporesponsiveness to exogenous ANG II in both early and adv anced cirrhosis, endogenous ANG II contributes to the maintenance of basal vascular tone only in advanced cirrhosis, These findings suggest a role of ANG II in the pathogenesis of ascites. Attenuated LBNP responses occurred o nly in advanced cirrhosis, without apparent interaction with endogenous ANG II.