标题：Berberine via suppression of transient receptor potential vanilloid 4 channel improves vascular stiffness in mice
作者：Wang, Jie; Guo, Tao; Peng, Qi-Sheng; Yue, Shou-Wei; Wang, Shuang-Xi
作者机构：[Wang, Jie; Guo, Tao; Wang, Shuang-Xi] Shandong Univ, Key Lab Cardiovasc Remodelling & Funct Res, Chinese Minist Educ, Qilu Hosp,Med Sch, Jinan, Shand 更多
通讯作者地址：[Wang, SX]Shandong Univ, Key Lab Cardiovasc Remodelling & Funct Res, Chinese Minist Educ, Qilu Hosp,Med Sch, Jinan, Shandong, Peoples R China.
来源：JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
关键词：berberine; transient receptor potential vanilloid 4; vascular smooth; muscle cells; blood pressure; vascular stiffness; ageing
摘要：Berberine, as an alkaloid found in many Chinese herbs, improves vascular functions in patients with cardiovascular diseases. We determined the effects of berberine in hypertension and vascular ageing, and elucidated the underlying mechanisms. In isolated aortas, berberine dose-dependently elicited aortic relaxation. In cultured cells, berberine induced the relaxation of vascular smooth muscle cells (VSMCs). Overexpression of transient receptor potential vanilloid 4 (TRPV4) channel by genetic approaches abolished the berberine-induced reduction in intracellular Ca2+ concentration in VSMCs and attenuated berberine-elicited vessel dilation in mice aortas. In deoxycorticosterone acetate (DOCA)-induced hypertensive model, treatment of mice with berberine or RN-1734, a pharmacological inhibitor of TRPV4, significantly decreased systemic blood pressure (BP) in control mice or mice infected with an adenovirus vector. However, berberine-induced effects of lowering BP were reversed by overexpressing TRPV4 in mice by infecting with adenovirus. Furthermore, long-term administration of berberine decreased mean BP and pulse BP, increased artery response to vasodilator and reduced vascular collagen content in aged mice deficient in apolipoprotein E (Apoe-KO), but not in Apoe-KO old mice with lentivirus-mediated overexpression of TRPV4 channel. In conclusion, berberine induces direct vasorelaxation to lower BP and reduces vascular stiffness in aged mice through suppression of TRPV4.