Abstract
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.
Highlights
Berberine, an isoquinoline alkaloid originally isolated from the Chinese herb Coptis chinensis, is an anti-microbial drug routinely prescribed for the treatment of diarrhoea in many Asian countries [1]
Vascular smooth muscle cells (VSMCs) contraction is predominantly regulated by myosin light chain (MLC), which is determined by increased intracellular Ca2+ ([Ca2+]i) concentration through calmodulin (CaM)-dependent MLC kinase, resulting in
We provide the first evidence that administration of berberine in vivo lowers high blood pressure (BP) in deoxycorticosterone acetate (DOCA)-induced hypertensive mice and reduces vascular stiffness in aged Apoe-KO mice
Summary
An isoquinoline alkaloid originally isolated from the Chinese herb Coptis chinensis, is an anti-microbial drug routinely prescribed for the treatment of diarrhoea in many Asian countries [1]. In this form it is reported to exert anti-fungal, anti-bacterial/viral and antioncogenic effects, as well as a beneficial effect on diabetes, atherosclerosis and hyperlipidemia [2, 3]. Our data in this study suggest that berberine induces endothelium-independent relaxations in VSMCs to lower BP and to delay vascular stiffness by suppressing TRPV4 and the associated Ca2+ signalling in mice.
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