Effect of Selective Blockade of β2-Adrener gis Receptors on Portal and Systemic Hemodynamics in a Portal Hypertensive Rat Model

Abstract

Propranolol, a nonselective beta-adrenergic blocker, appears to reduce portal pressures in portal hypertension by reducing portal blood flow. The aim of this study was to investigate the relative role of selective beta 1- and beta 2-blocking properties of propranolol participating in portal blood flow reduction. Portal hypertensive rats receiving placebo exhibited elevated portal blood flow of 1.31 +/- 0.4 ml/min per g splanchnic tissue and portal pressure of 15.4 +/- 0.43 mmHg, with elevated cardiac index of 358 +/- 20 ml/min per kg. Portal hypertensive rats were divided into groups receiving propranolol nonspecific beta-blockade, atenolol selective beta 1-blockade, and ICI 118551 selective beta 2-blockade. Significant (p less than 0.05) reductions in portal blood flow of 32%, 27%, and 21% were achieved in all three groups, respectively, accompanied by significant (p less than 0.05) reductions in portal pressure of 1.7 +/- 0.3, 0.9 +/- 0.2, and 0.8 +/- 0.2 mmHg, respectively. Cardiac index was significantly reduced in the propranolol-treated (25%) and atenolol-treated (20%) groups, but remained unchanged in the ICI 118551-treated group. We conclude that propranolol appears to achieve its therapeutic reduction in portal blood flow and portal pressure through combined participation of beta 1- and beta 2-adrenergic blockade. Furthermore, ICI 118551 selective beta 2-adrenergic blockade offers portal blood flow and portal pressure reduction independent of reduction in cardiac output, which could be uniquely advantageous in situations where impairment of cardiac compensatory mechanisms might prove deleterious.