Chronic administration of propranolol improves vascular contractile responsiveness in portal hypertensive rats

Propranolol is used clinically as a prophylactic drug to prevent oesophageal variceal bleeding in cirrhotic patients with portal hypertension. Vascular hyporesponsiveness is a common characteristic of the portal hypertensive state. The present study aimed to investigate whether chronic administration of propranolol could improve vascular responsiveness in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation (PVL). Sham-operated rats served as controls. There were four study groups: PVL-propranolol group (portal hypertensive rats receiving propranolol), PVL-vehicle group (portal hypertensive rats receiving saline), sham-propranolol group (sham-operated rats receiving propranolol) and sham-vehicle group (sham-operated rats receiving saline). Propranolol (30 mg kg-1 day-1) or saline was given for 9 days via gastric gavage starting 1 day before ligation and thereafter. Then, the superior mesenteric artery was removed from each group for contractile study after haemodynamic measurement. In portal hypertensive rats, propranolol significantly alleviated the hyperdynamic state, including portal pressure, cardiac index and total peripheral resistance in the treated group compared with the vehicle group. The maximal contractile responses to KCl and vasopressin in mesenteric artery were significantly greater in the sham-vehicle group than in the PVL-vehicle group. Long-term propranolol treatment enhanced the contractile reactivity of mesenteric artery to KCl and vasopressin in PVL rats, and the contractile profiles were corrected towards those in sham-treated animals. In contrast, propranolol treatment decreased heart rate, mean arterial pressure and cardiac index but did not alter the contractile responsiveness of sham-operated rats. These results showed that, in portal vein stenosed rats, long-term treatment with propranolol improved arterial contractile reactivity together with portal pressure reduction. The propranolol effect on vascular reactivity is probably related to haemodynamic improvement, instead of a direct contractile effect on the vasculature.