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Altered peripheral vascular responses to exogenous and endogenous endothelin-l in patients with well-compensated cirrhosis

Helmy, A; Jalan, R; Newby, DE; Johnston, NR; Hayes, PC; Webb, DJ; (2001) Altered peripheral vascular responses to exogenous and endogenous endothelin-l in patients with well-compensated cirrhosis. HEPATOLOGY , 33 (4) 826 - 831. 10.1053/jhep.2001.23502.

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Abstract

Plasma endothelin concentrations are elevated in cirrhosis and correlate with disease severity. This study assessed forearm vascular responses to exogenous endothelin-1 (ET-1), and evaluated the contribution of endogenous ET-1 to the maintenance of basal peripheral vascular tone in patients with well-compensated cirrhosis (n = 11) and matched healthy controls (n = 8). Bilateral forearm blood flow (FBF) was measured at baseline and following unilateral, subsystemic, intrabrachial artery infusions of ET-1 (2 and 6 pmol/min); BQ-123, a selective ETA receptor antagonist (3 and 10 nmol/min); and BQ-788, a selective ETB receptor antagonist (0.3 and 1 nmol/min) using venous occlusion plethysmography. Baseline systemic hemodynamics and plasma ET-1 and big ET-1 concentrations were measured using electrical bioimpedance and radioimmunoassay, respectively. Patients and controls had similar baseline FBF, systemic hemodynamics, and plasma ET-1 and big ET-1 concentrations. In both groups, ET-1 and BQ-788 caused significant vasoconstriction (P < .001) and BQ-123 caused significant vasodilatation (P < .001). Compared with controls, cirrhotic patients had attenuated ET-1 responses (P < .001), augmented BQ-123 responses (P < .001), and similar BQ-788 responses (P = .62). Despite normal systemic hemodynamics and plasma ET-1 concentrations, forearm vascular responses to exogenous ET-1 are reduced in cirrhotic patients. The augmented vasodilatation to BQ-123 in cirrhotic patients is consistent with a compensated vasodilated state, and a greater contribution of ET-1 to the maintenance of basal vascular tone acting through the ETA receptor.

Type:Article
Title:Altered peripheral vascular responses to exogenous and endogenous endothelin-l in patients with well-compensated cirrhosis
DOI:10.1053/jhep.2001.23502
Keywords:VESSELS IN-VIVO, PLASMA ENDOTHELIN, CARDIAC-OUTPUT, LIVER-DISEASE, NITRIC-OXIDE, SPLANCHNIC HEMODYNAMICS, ELECTRICAL BIOIMPEDANCE, CLINICAL-SIGNIFICANCE, HEPATORENAL-SYNDROME, HUMAN RESISTANCE

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