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Keywords:

  • terlipressin - α1-adrenoceptor antagonist - portal hypertension - hemodynamics

Abstract: Aims/Background: The purpose of this study was to investigate the therapeutic effects of terlipressin, alone or in combination with DL-028, a synthetic α1-adrenoceptor antagonist on anesthetized portal hypertensive rats. Methods: Portal hypertension was induced by either partial portal vein ligation (PVL) or bile duct ligation (BDL) in Sprague-Dawley rats. Each portal hypertensive rat received only one of the two regimens: vehicle plus terlipressin or DL-028 plus terlipressin. Terlipressin dosage was 0.017 mg/kg/min infused for 3 min, while vehicle or DL-028 (0.50 μg/kg/min) was continuously infused for 40 min, starting 10 min before terlipressin infusion. Results: In PVL rats, infusions of vehicle plus terlipressin induced significant, maximum reduction of portal venous pressure (PVP, – 11.0±1.8%) and prominent elevation of mean arterial pressure (MAP, 50.3±9.0%) from baseline. Infusions of DL-028 plus terlipressin induced maximum PVP reduction (–17.5±2.8%) and MAP elevation (39.8±7.4%). In BDL rats, infusions of vehicle plus terlipressin also induced significant, maximum reduction of PVP (–6.8±2.1%) and prominent elevation of MAP (61.4±7.8%) from baseline. Infusions of DL-028 plus terlipressin induced maximum PVP reduction (–17.9±2.2%) and MAP elevation (47.9±7.4%). Compared to vehicle plus terlipressin, DL-028 significantly enhanced portal hypotensive effects of and attenuated systemic pressor effects of terlipressin in both PVL and BDL rats. Conclusions: Our results suggest that terlipressin, alone or in combination with DL-028, induced portal hypotensive effects in portal hypertensive rats. The combination of terlipressin with DL-028 was beneficial in enhancing the portal hypotensive effects and ameliorating the systemic pressor effects of terlipressin.