Hemodynamic Effects of Chronic Tetrandrine and Propranolol Administration on Portal Hypertensive Rats

Abstract

The purpose of this study was to investigate the therapeutic effects of tetrandrine and propranolol, alone or in combination, on portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Animals were allocated into one of the four groups: vehicle group (0.1 N HC1, 0.7 ml/day), tetrandrine group (50 mg/kg/ day), propranolol group (30 mg/kg/day), and tetrandrine (50 mg/kg/day) plus propranolol (30 mg/kg/day) group. Drug or vehicle was administered by gavage for consecutive 9 days. After 9 days of treatment, the portal venous pressure and mean arterial pressure in each treatment group were significantly lower than those in the vehicle group. The cardiac index was not changed by tetrandrine alone, but reduced in the two groups receiving propranolol alone or in combination. Total peripheral resistance was significantly decreased in the tetrandrine group and significantly increased in the tetrandrine plus propranolol group as compared with the vehicle group. Our results suggested that tetrandrine or propranolol alone induced portal hypotensive effects, with propranolol achieving better antihyperdynamic effects in terms of cardiac index, and in combination propranolol effects predominated over those of tetrandrine.

Tetrandrine

“…By repeated administration to rats with portal hyper-tension, tetrandrine (10 to 50 m g k g by gavage, b i d . for 8 to 9 d) reduces portal hypertension and ameliorates splanchnic hyperemia (43,44).…”

Hemodynamic Effects of Synephrine Treatment in Portal Hypertensive Rats

“…However, administration of "vasodilating" portal hypotensive drugs such as organic nitrates (22), prazosin (23), verapamil (26), tetrandrine (27) or tetramethylpyrazine (28) did have inadvertent side effects in terms of further reduction in systemic arterial pressure or resistance in cirrhotic or portal hypotensive animals. In contrast, synephrine administration exerted the distinct advantage of improving the systemic vasodilative state in portal hypertensive animals, even compared with propranolol (18 -20) or octreotide (14,20,21). On the other hand, the magnitude of reduction in PVP and PTBF by synephrine in PVL rats was smaller than that by propranolol (32% and 39%, respectively) or octreotide (28% and 68%, respectively) (20), indicating that synephrine at 1 mg/ kg per 12 h is not as efficacious as propranolol at 30 mg/ kg per day or octreotide at 100 mg /kg per 12 h. As the present study and previous studies have shown, it seems paradoxical that both the a1-adrenoceptor agonist synephrine and the a 1-adrenoceptor antagonist prazosin (2,3,23) can ameliorate portal hypertension and splanchnic hyperemia in portal hypertensive animals.…”

“…In contrast, synephrine administration exerted the distinct advantage of improving the systemic vasodilative state in portal hypertensive animals, even compared with propranolol (18 -20) or octreotide (14,20,21). On the other hand, the magnitude of reduction in PVP and PTBF by synephrine in PVL rats was smaller than that by propranolol (32% and 39%, respectively) or octreotide (28% and 68%, respectively) (20), indicating that synephrine at 1 mg/ kg per 12 h is not as efficacious as propranolol at 30 mg/ kg per day or octreotide at 100 mg /kg per 12 h. As the present study and previous studies have shown, it seems paradoxical that both the a1-adrenoceptor agonist synephrine and the a 1-adrenoceptor antagonist prazosin (2,3,23) can ameliorate portal hypertension and splanchnic hyperemia in portal hypertensive animals. Synephrine is a vasoconstrictor of mesenteric arteries (6) and probably exerts its portal hypotensive effects through splanchnic vasoconstriction and thereby reducing PTBF, whereas prazosin probably exerts its portal hypotensive effects through reducing intrahepatic and porto-systemic vascular resistances.…”

“…The degree of reduction by synephrine in PVP and PTBF (-19.5% and -20.4%) was similar in PVL and BDL rats, while the degree of enhancement in MAR (10.4% and 23.4%), SVR (26.3% and 51.0%) and PTVR (47.1% and 67.7%) tended to be less in PVL rats than in BDL rats. It has been reported that repeated administration of portal hypotensive drugs such as propranolol (18 -20), octreotide (14,20,21), organic nitrates (22), prazosin (23), clonidine (24), verapamil (25,26), tetrandrine (27) or tetramethylpyrazine (28) into cirrhotic or portal hypertensive animals also leads to amelioration of portal hypertension or splanchnic hyperemia. However, administration of "vasodilating" portal hypotensive drugs such as organic nitrates (22), prazosin (23), verapamil (26), tetrandrine (27) or tetramethylpyrazine (28) did have inadvertent side effects in terms of further reduction in systemic arterial pressure or resistance in cirrhotic or portal hypotensive animals.…”

Effects and Interactions of Ginger and Propranolol in Pre-Hepatic Portal Hypertensive Rats

“…Propranolol administration was started one day before PPVL [19]. Ginger doses were given for 30 days before PVL [20].…”