Anti-hypertensive and Vasodilatory Effects of Qingda Granules by Suppression of Calcium Influx and the AKT Pathway.

The Qingda granule (QDG) formulation was simplified from the Qingxuan Jiangya Decoction, which has been used in China to treat hypertension for decades. However, the molecular mechanisms of QDG in antihypertension remain largely unknown. Therefore, we evaluated the therapeutic efficacy of QDG against elevated blood pressure and explored its underlying mechanism. QDG treatment decreased elevated blood pressure and increased the vascular elasticity of thoracic aortic rings to KCl stimulation in spontaneously hypertensive rats. QDG treatment increased the relaxation of isolated thoracic aortic rings precontracted with norepinephrine (NE) or KCl in an endothelium-independent manner, which was attenuated by treatment with verapamil, but not by treatment with TEA, 4-AP, Gli, or BaCl2. Moreover, QDG pretreatment attenuated the CaCl2-induced constriction of isolated thoracic aortic rings in K+- or NE-containing Ca2+-free solutions. In addition, QDG pretreatment significantly inhibited the influx of Ca2+ in A7r5 cells induced by a K+- or NE-containing Ca2+ solution and decreased the levels of p-AKT but had no effect on levels of total AKT protein in isolated thoracic aortic rings. Considering these results, QDG treatment attenuated elevated blood pressure and promoted the vasorelaxation of thoracic aortic rings by inhibiting the influx of Ca2+ and activating the AKT pathway.