Tsai Hsin-Hung, Chen Ing-Jun, Lo Yi-Ching
Department of Pharmacology College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
J Ethnopharmacol. 2008 May 22;117(3):457-62. doi: 10.1016/j.jep.2008.02.024. Epub 2008 Feb 23.
San-Huang-Xie-Xin-Tang (SHXT), composed of Coptidis rhizoma, Scutellariae radix and Rhei rhizoma, is traditionally used to treat hypertension.
Our aim was to investigate the pharmacology effect of SHXT on a thromboxane A(2) analogue U46619-induced increase in pulmonary hypertension and protein expression in primary pulmonary smooth muscle cells (PASMCs).
Arterial blood pressure and isometric tension in the aorta and pulmonary artery of rats were measured by pressure and force transducers, respectively. Protein expressions on PASMCs were detected by Western blotting.
SHXT significantly attenuated U46619-induced increase in arterial blood pressure. The inhibitory effect of SHXT on pulmonary arterial pressure was greater than systemic arterial pressure in U46619 treated rats. Similarly, the inhibitory effect of SHXT on U46619-induced vasoconstriction in rat pulmonary arterial rings was greater than that in aortic rings. In U46619 treated PASMCs, SHXT down-regulated expression of phosphodiesterase type 5 (PDE5), Rho-kinase (ROCK) II, cyclooxygenase-2 (COX-2) and up-regulated expression of soluble guanylyl cyclase (sGC) alpha(1) and sGCbeta(1).
SHXT attenuated U46619-induced increase in systemic and pulmonary arterial blood pressure. Inhibition of PDE5, ROCK-II, COX-2 and stimulation of sGC may play important roles in the cardiovascular effects of SHXT.
三黄泻心汤由黄连、黄芩和大黄组成,传统上用于治疗高血压。
我们的目的是研究三黄泻心汤对血栓素A2类似物U46619诱导的肺动脉高压升高及原代肺平滑肌细胞(PASMCs)中蛋白表达的药理学作用。
分别通过压力和力传感器测量大鼠主动脉和肺动脉的动脉血压及等长张力。通过蛋白质印迹法检测PASMCs上的蛋白表达。
三黄泻心汤显著减轻U46619诱导的动脉血压升高。在U46619处理的大鼠中,三黄泻心汤对肺动脉压的抑制作用大于体动脉压。同样,三黄泻心汤对U46619诱导的大鼠肺动脉环血管收缩的抑制作用大于主动脉环。在U46619处理的PASMCs中,三黄泻心汤下调5型磷酸二酯酶(PDE5)、Rho激酶(ROCK)II、环氧化酶-2(COX-2)的表达,并上调可溶性鸟苷酸环化酶(sGC)α1和sGCβ1的表达。
三黄泻心汤减轻U46619诱导的体动脉和肺动脉血压升高。抑制PDE5、ROCK-II、COX-2以及刺激sGC可能在三黄泻心汤的心血管效应中起重要作用。