Effects of San-Huang-Xie-Xin-Tang on U46619-induced increase in pulmonary arterial blood pressure.
BACKGROUND
San-Huang-Xie-Xin-Tang (SHXT), composed of Coptidis rhizoma, Scutellariae radix and Rhei rhizoma, is traditionally used to treat hypertension.


OBJECTIVE
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).


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Tsai
Hsin-Hung
HH
Department of Pharmacology College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Chen
Ing-Jun
IJ
Lo
Yi-Ching
YC
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D015153:Blotting, Western; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents; D054460:rho-Associated Kinases / Q000096:biosynthesis / Q000235:genetics
D004365:Drugs, Chinese Herbal; C501029:San-Huang-Xie-Xin-Tang; D014662:Vasoconstrictor Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D051546:Cyclooxygenase 2; D054460:rho-Associated Kinases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5