Beneficial effects of combined terlipressin and tetramethylpyrazine administration on portal hypertensive rats

Abstract

The purpose of this study was to investigate the therapeutic effects of terlipressin (TP) alone or in combination with tetramethylpyrazine (TMP) on anesthetized portal hypertensive rats. Portal hypertension was induced by either partial portal vein ligation (PVL, without cirrhosis) or bile duct ligation (BDL, with cirrhosis) in Sprague-Dawley rats. Each PVL or BDL rat received only one of the two regimens: vehicle for 3 min followed by TP (0.017 mg x kg(-1) x min(-1) for 3 min) or TMP (10 mg x kg(-1) x min(-1) for 3 min) followed by TP. In PVL rats, infusion of vehicle followed by TP induced significant reduction of portal venous pressure (PVP, -15.0+/-1.0%) and prominent elevation of mean arterial pressure (MAP, 57.3+/-8.1%) as well as total peripheral resistance (TPR, 113+/-11%) from baseline, and there was a cardiodepressant response (cardiac index, CI, -26.3+/-1.1%). Infusion of TMP followed by TP induced significant reduction of PVP (-20.3+/-0.4%) and CI (-9.9+/-1.2%) and significant elevation of MAP (31.3+/-2.5%) and TPR (46.0+/-4.1%) from baseline. In BDL rats, infusion of vehicle followed by TP also induced significant reduction of PVP (-13.8+/-1.7%) but an increase in MAP (57.1+/-2.2%) and TPR (101+/-6%) from baseline, and there also was a cardiodepressant response (CI, -21.4+/-2.3%). Infusion of TMP followed by TP induced significant reduction of PVP (-18.9+/-1.4%) and CI (-11.9+/-2.1%), but an increase in MAP (36.2+/-2.5%) and TPR (55.0+/-5.2%). Compared with vehicle followed by TP, TMP not only significantly enhanced portal hypotensive (PVP reduction) effects of TP but also attenuated the systemic pressor (MAP and TPR elevation) and cardiodepressant (CI reduction) effects of TP in both PVL and BDL rats. Our results suggest that TP, alone or in combination with TMP, induced portal hypotensive effects in two models of portal hypertensive rats. Combination of TP and TMP was beneficial in enhancing portal hypotensive effects of TP and ameliorating the systemic pressor and cardiodepressant effects of TP.

Process optimization and characterization of fragrant oil from red pepper (Capsicum annuumL.) seed extracted by subcritical butane extraction

“…Pyrazine volatiles are mostly responsible for roasted, nutty, caramel and similar aroma/flavor descriptions . In addition, 2,3,5,6‐tetramethylpyrazine (TMP) is a biologically active ingredient that has been found to have significant therapeutic activity, including improving brain microcirculation, inhibiting thrombus formation, decreasing platelet aggregation and improving blood viscosity . It was reported recently that TMP has appreciable blood–brain barrier (BBB) penetrability …”

Hemodynamic effects of Salvia miltiorrhiza on cirrhotic rats

“…Common bile duct ligation was performed in male Sprague-Dawley rats (250-300 g) to induce hepatic fibrosis and portal hypertension (Kountouras et al 1981), as previously described (Chang et al 1999). Rats were anesthetized with ether.…”

Ligustrazine formation in Zhenjiang aromatic vinegar: changes during fermentation and storing process

“…In our previous study, Zhenjiang aromatic vinegar was found to possess antioxidant activity, which was due to the common action of flavonoids, polyphenols, amino acids and organic acids, as well as ligustrazine (2,3,5,6‐tetramethylpyrazine) and melanoidins 6–8. Among these compounds, ligustrazine, which is a bioactive alkaloid originally isolated from the traditional Chinese medicine Ligusticum chuanxiong Hort., has attracted much public interest because of its potent bioactivities, such as curing cardiovascular and cerebrovascular diseases and hypertension 9–11…”