Hemodynamic effects of terbutaline, a β2-adrenoceptor agonist, in conscious rats with secondary biliary cirrhosis

Abstract

The hemodynamic responses to terbutaline - a selective beta 2-adrenoceptor agonist - were studied in conscious normal rats and in conscious rats with secondary biliary cirrhosis. Compared with those of normal rats, dose-response curves in cirrhotic rats indicated significantly decreased reactivity in arterial pressure and heart rate. Half-maximal effective dose was not significantly different between the two groups. Terbutaline induced significant, dose-dependent decreases in portal pressure in both normal rats (9.3%) and cirrhotic rats (13.8%). In normal rats, terbutaline administration (32 micrograms.min-1.kg-1 body wt) increased both cardiac output and portal tributary blood flow, thus mimicking hemodynamic changes in cirrhotic rats. In cirrhotic rats, despite a significant increase in portal tributary blood flow (from 19.9 +/- 1.7 ml/min to 22.7 +/- 1.5 ml/min), terbutaline decreased portal pressure from 17.4 +/- 1.0 mm Hg to 15.0 +/- 0.8 mm Hg. This study indicates that increased beta 2-adrenoceptor stimulation in cirrhotic rats may be involved in hyperdynamic circulation. The association of a decreased portal pressure and increased splanchnic blood flow suggests that beta 2-adrenoceptor stimulation may modulate hepatic and portal collateral vascular resistance.

Vasoactive factors and hemodynamic mechanisms in the pathophysiology of portal hypertension in cirrhosis

“…Substances like norepinephrine, substance P, thrombin, angiotensin II, (Schneider et al, 1999), endothelin (Jimenez and Rodes, 1994), prostanoids (Graupera et al, 2003) influence the contractile tone of myofibroblasts increasing portal resistance. By pharmacologically modifying the tone of myofibroblasts, a reduction in intrahepatic resistance is obtainable (Bhathal and Groszmann, 1985;Poo et al, 1992). The pivotal pathophysiological mechanism contributing to the dynamic increase in intrahepatic resistance is an endothelial dysfunction (Matei et al, 2006).…”