Anti-hypertensive and vasodilatory effects of amended Banxia Baizhu Tianma Tang

Although Banxia Baizhu Tianma Tang (BBT) has been long administered for hypertensive treatment in Traditional Chinese Medicine (TCM), the ratio of the herbal components that makes up the formulation has not been optimized with respect to the anti-hypertensive effect that it inherently possesses. A newly amended BBT (ABBT) formulation was developed using the evidence-based approach of orthogonal stimulus-response compatibility model. The ABBT showed enhanced therapeutic effect while maintaining its traditional theoretical approach rooted in TCM. This study was designed to investigate the possible mechanism of actions involved in the vasodilatory activity of ABBT-50 by evaluating its vasodilative effect on isolated Sprague Dawley rats in the presence of absence of various antagonists. When pre-contracted with phenylephrine, relaxation was observed in endothelium intact (EC50= 0.027 +/- 0.003 mg/ml, R-max = 109.8 +/- 2.12%) and denuded aortic rings (EC50 = 0.409 +/- 0.073 mg/ml, R-max = 63.15 +/- 1.78%), as well as in endothelium intact aortic rings pre-contracted with potassium chloride (EC50 = 32.7 +/- 12.16 mg/ml, R-max = 34.02 +/- 3.82%). Significant decrease in the vasodilative effect of ABBT-50 was observed in the presence of N omega-nitro-L-arginine methyl ester (EC50 = 0.12 +/- 0.021 mg/ml, R-max = 75.33 +/- 3.28%), 1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one (EC50 = 0.463 +/- 0.18 mg/ml, R-max = 54.48 +/- 2.02%), methylene blue (EC50 = 0.19 +/- 0.037 mg/ml, R-max = 83.69 +/- 3.19%), indomethacin (EC50= 0.313 +/- 0.046 mg/ml, R-max = 71.33 +/- 4.12%), atropine (EC50 = 0.146 +/- 0.013 mg/ml, R-max = 77.2 +/- 3.41%), and 4-aminopyridine (EC50= 0.045 +/- 0.008 mg/ml, R-max = 95.55 +/- 2.36%). ABBT-50 was also suppressing Ca2+ release from sarcoplasmic reticulum and inhibiting calcium channels. Vasodilatory effects of ABBT-50 are mediated through NO/sGC/cGMP cascade and PGI2, followed by muscarinic pathways and calcium channels.