The prehepatic portal hypertensive rat is a model of human portal hypertension. It is widely used due to the fact that portosystemic shunting develops consistently. Bleeding from oesophageal varices is a frequent, life-threatening, complication in patients with portal hypertension. There are conflicting reports that prostacyclin is the main mediator. It is not the main mediator of the hyperdynamic circulation in portal hypertensive rats. Prostacyclin increases cardiac output and portal pressure in control and portal vein ligated rats, but the effects were diminished in cirrhotic rats, suggesting down regulation and involvement of prostacyclin in cirrhosis. Block of the enzyme cyclooxygenase can cause constriction of the mesenteric artery in vivo in the portal vein ligated rat. This suggests the role of prostacyclin. In this study, BAY 73-1449 is a selective antagonist of the prostacyclin receptor (IP), with an IC50 of less than 0.1 nM.
BAY 73-1449 is a selective antagonist of prostacyclin receptor, with high potency in cAMP assays in Human HEL cells and rat DRG. Moreover, it has the potential for the research of lowering blood pressure. In studies in vivo, BAY 73-1449 (1 mg/kg) is effective in the rat natural voiding model, with efficacy for over 8 hours. BAY 73-1449 does not significantly reduce mesenteric inflow, but significantly reduces splenic shunt vessel outflow in rats. In addition, it has no effects on the degree of portosystemic shunting in rats. BAY 73-1449 has no effects on portal pressures in rats.
In summary, BAY 73-1449 selectively constricts shunt vessels to reduce shunt vessel flow. It can acutely reduce shunt vessel blood flow in portal hypertensive rats.
Bexis S, et, al. Eur J Pharmacol. 2008 Aug 20;590(1-3):322-6.