Hemodynamic effects of acute tetrandrine and terlipressin administration on portal hypertensive rats

Abstract

The purpose of this study was to investigate the therapeutic effects of tetrandrine and terlipressin, alone or in combination, on anesthetized portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Each portal hypertensive rat received one of three regimens: vehicle plus terlipressin, tetrandrine (.50 mg.kg-1.min-1) [corrected] plus terlipressin, or tetrandrine (.75 mg.kg-1.min-1) [corrected] plus terlipressin. Terlipressin dosage was 0.025 mg.kg-1.min-1 [corrected] infused for 3 min. Infusion of vehicle followed by terlipressin induced significant reduction of portal venous pressure (PVP, -24.3 +/- 1.5%) and prominent elevation of mean arterial pressure (MAP, 73.3 +/- 4.6%) as well as total peripheral resistance (TPR, 133 +/- 8%) from baseline, and there was a cardiodepressant response (cardiac index, CI, -30.6 +/- 3.8%; heart rate, HR, -10.4 +/- 2.1%). Infusion of tetrandrine (.50 mg.kg-1.min-1) [corrected] induced significant reduction of PVP (-7.2 +/- 0.9%), MAP (-12.5 +/- 1.6%), and TPR (-14.3 +/- 4.2%) from baseline. Infusions of tetrandrine followed by terlipressin induced significant reduction of PVP (-14.2 +/- 2.4%) but an increase in MAP (22.6 +/- 2.7%) and TPR (71.1 +/- 10.5%). Infusion of tetrandrine (.75 mg.kg-1.min-1) [corrected] induced significant reduction of PVP (-9.9 +/- 0.8%). MAP (-19.2 +/- 2.1%), and TPR (-24.1 +/- 2.1%) from baseline. Infusions of tetrandrine followed by terlipressin induced significant reduction of PVP (-14.0 +/- 1.1%) but an increase in MAP (14.0 +/- 2.7%) and TPR (75.2 +/- 5.2%). Compared with vehicle followed by terlipressin, tetrandrine significantly attenuated systemic pressor (MAP and TPR elevation), cardiodepressant (CI reduction) as well as portal hypotensive (PVP reduction) effects of terlipressin. Our results suggest that tetrandrine and terlipressin, alone or in combination, induced portal hypotensive effects in portal hypertensive rats. Combined tetrandrine and terlipressin administration ameliorated systemic pressor and cardiodepressant effects of terlipressin, but it also attenuated the latter's portal hypotensive effects.