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

Plasma endothelin concentrations are elevated in cirrhosis and correlate wi th disease severity. This study assessed forearm vascular responses to exog enous endothelin-1 (ET-1), and evaluated the contribution of endogenous ET- 1 to the maintenance of basal peripheral vascular tone in patients with wel l-compensated cirrhosis (n = 11) and matched healthy controls (n = 8). Bila teral forearm blood flow (FBF) was measured at baseline and following unila teral, subsystemic, intrabrachial artery infusions of ET-1 (2 and 6 pmol/mi n); 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. I n both groups, ET-1 and BQ-788 caused significant vasoconstriction (P < .00 1) and BQ-123 caused significant vasodilatation (P < .001). Compared with c ontrols, cirrhotic patients had attenuated ET-1 responses (P < .001), augme nted BQ-123 responses (P < .001), and similar BQ-788 responses (P = .62). D espite normal systemic hemodynamics and plasma ET-1 concentrations, forearm vascular responses to exogenous ET-1 are reduced in cirrhotic patients. Th e augmented vasodilatation to BQ-123 in cirrhotic patients is consistent wi th a compensated vasodilated state, and a greater contribution of ET-1 to t he maintenance of basal vascular tone acting through the ETA receptor.