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

Background and Aims: The renin-angiotensin and sympathetic nervous systems are activated in cirrhosis. This study aimed to establish the role of angiotensin II (ANG II) in the regulation of basal and sympathetically stimulated vascular tone in preascitic cirrhotic patients and patients with diuretic-refractory ascites compared with age- and sex-matched healthy controls Methods: Forearm blood flow (FBF) responses to lower body negative pressure (LBNP) and to subsystemic, intrabrachial infusions of losartan, an angiotensin II type 1 (AT1) receptor antagonist, norepinephrine, and ANG II were measured using venous occlusion plethysmography. Results: In all groups, ANG II and norepinephrine caused dose-dependent reductions in FBF (P < 0.001); responses to norepinephrine were similar across the 3 groups but those to ANG II were less in both cirrhotic groups than in controls (P < 0.01). Losartan caused a dose-dependent increase in FBF only in patients with refractory ascites (P < 0.01). LBNP caused less reduction in FBF in refractory ascites patients than in both preascitic patients and controls (P < 0.01). Conclusions: Despite hyporesponsiveness to exogenous ANG II in both early and advanced 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 only in advanced cirrhosis, without apparent interaction with endogenous ANG II.