RESUMO
AIM: To investigate the effects of Glytan on splanchnic hemodynamics and its reduction of portal pressure in portal hypertensive rats. METHODS: Glytan (Ganluotong in Chinese), is composed of salvianolic acid B and diammonium glycyrrhizinate. Portal hypertension (PHT) was induced in the rats by common bile duct ligation (BDL). Hemodynamic studies were performed using the colored microsphere method. Radioimmunoassay (RIA) was used to determine endothelin (ET)-1 levels in the mesenteric circulation. Western blotting methods were used to investigate the effect of Glytan on ET A receptor (ETAR), ET B receptor (ETBR), endothelial NO synthase (eNOS), G-protein-coupled receptor kinase (GRK)2, and ß-arrestin 2 expression in the mesentery. The mRNA of ETAR and ETBR was determined using real-time polymerase chain reaction. RESULTS: Treatment with Glytan reduced portal pressure (PP) and portal territory blood flow (PTBF) and increased both mean arterial pressure (MAP) and splanchnic vascular resistance (SVR). Especially at 4 wk, PP decreased by about 40%, while MAP increased by 13%, SVR increased by 12%, and PTBF decreased by about 21%. The effect of blood flow reduction was greatest in the mesentery (about 33%) at 4 wk. The mesenteric circulation ET-1 levels of BDL rats were lower and negatively correlated with PP at 4 wk. Glytan can increase mesenteric ET-1 content and inhibit ETBR, eNOS, GRK2, and ß-arrestin 2 expression in the mesentery. Moreover, Glytan showed no effect on the expression of ETAR protein and mRNA. CONCLUSION: The decreased PP and PTBF observed after Glytan treatment were related to increased mesenteric vasoconstriction and increased receptor sensitivity to vasoconstrictor.
Assuntos
Benzofuranos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Ácido Glicirretínico/análogos & derivados , Hipertensão Portal/tratamento farmacológico , Mesentério/irrigação sanguínea , Mesentério/efeitos dos fármacos , Pressão na Veia Porta/efeitos dos fármacos , Circulação Esplâncnica/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia , Animais , Velocidade do Fluxo Sanguíneo , Modelos Animais de Doenças , Antagonistas do Receptor de Endotelina B/farmacologia , Endotelina-1/sangue , Quinase 2 de Receptor Acoplado a Proteína G/antagonistas & inibidores , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Ácido Glicirretínico/farmacologia , Hipertensão Portal/sangue , Hipertensão Portal/enzimologia , Hipertensão Portal/fisiopatologia , Masculino , Mesentério/enzimologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Ratos Sprague-Dawley , Receptor de Endotelina B/efeitos dos fármacos , Receptor de Endotelina B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de TempoRESUMO
The effects of ulinastatin (UST) and methyl prednisolone (MPS) on endotoxin induced shock were compared by the criterion of microcirculation dynamics in rat mesenterium and plasma phospholipase A2 (PLA2) activity in modified Shwartzman reaction model. The mean arterial pressure and red cell velocity were well maintained when MPS was administered during endotoxin induced shock. In the case of UST, superior anti-shock effects, indicated by reduced vasoconstriction, were obtained when it was administered prior to endotoxin induced shock. The anti-shock effect of UST, similar to MPS, was supported by the change of serum PLA2 activity. Therefore, concerning the administration timing of anti-shock drugs, MPS should be administered after shock occurs, and UST is most effective as a prophylactic treatment. UST has an anti-shock effect like steroid hormone.