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

“…46 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. 47 It was reported recently that TMP has appreciable blood-brain barrier (BBB) penetrability. 48…”

Assessment of the Anti-anginal Effect of Tetramethylpyrazine Using Vasopressin-Induced Angina Model Rats

“…7) Intracoronary administration of vasopressin has been shown to constrict small coronary arteries, causing subendocardial ischemia 9) and Ca 2+ channel blocker is known to possess a potent coronary vasodilator effect, which has been widely used for patients with vasospastic angina. 1) Tetramethylpyrazine significantly inhibited the vasopressin-induced subendocardial ischemia, which was not observed by the vehicle, indicating that tetramethylpyrazine may possess an anti-ischemic effect.…”

“…6) Moreover, pretreatment of tetramethylpyrazine was shown to ameliorate a vasoconstrictor terlipressin-induced decrease of cardiac index in portal hypertensive rats. 7) However, in vivo experimental evidence for empirically known clinical efficacy of tetramethylpyrazine is still limited. In the present study, we assessed the effects of tetramethylpyrazine on the vasopressin-induced angina model of rats, which has been shown to be useful and reliable in evaluating the anti-spastic effect of a drug in vivo.…”

“…was infused over 1 min. The dose of tetramethylpyrazine in this study was determined by previous experimental studies [2][3][4][5][6][7] as well as clinical experiences as a traditional Chinese medicine.…”

Hemodynamic Effects of Synephrine Treatment in Portal Hypertensive Rats

“…Portal hypertension with cirrhosis was induced by bile duct ligation, according to the method of Kountouras et al (12) and as previously reported (13). Briefly, male Sprague-Dawley rats (230 -280 g) were anesthetized with ether.…”