Altered peripheral vascular responses to exogenous and endogenous endothelin-1 in patients with well-compensated cirrhosis

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 ET_A receptor antagonist (3 and 10 nmol/min); and BQ‐788, a selective ET_B 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 ET_A receptor.