title: Berberine improves endothelial function by inhibiting endoplasmic reticulum stress in the carotid arteries of spontaneously hypertensive rats.
abstract: Activation of endoplasmic reticulum (ER) stress in endothelial cells leads to increased oxidative stress and often results in cell death, which has been implicated in hypertension. The present study investigated the effects of berberine, a botanical alkaloid purified from Coptidis rhizoma, on ER stress in spontaneously hypertensive rats (SHRs) and the underling mechanism. Isolated carotid arteries from normotensive WKYs and SHRs were suspended in myograph for isometric force measurement. Protein phosphorylations and expressions were determined by Western blotting. Reactive oxygen species (ROS) level was measured by DHE staining. SHR carotid arteries exhibited exaggerated acetylcholine-triggered endothelium-dependent contractions (EDCs) and elevated ROS accumulation compared with WKY arteries. Moreover, Western blot analysis revealed the reduced AMPK phosphorylation, increased eIF2α phosphorylation, and elevated levels of ATF3, ATF6, XBP1 and COX-2 in SHR carotid arteries while these pathological alterations were reversed by 12 h-incubation with berberine. Furthermore, AMPK inhibitor compound C or dominant negative AMPK adenovirus inhibited the effects of berberine on above-mentioned marker proteins and EDCs. More importantly, ROS scavengers, tempol and tiron plus DETCA, or ER stress inhibitors, 4-PBA and TUCDA normalized the elevated levels of ROS and COX-2 expression, and attenuated EDCs in SHR arteries. Taken together, the present results suggest that berberine reduces EDCs likely through activating AMPK, thus inhibiting ER stress and subsequently scavenging ROS leading to COX-2 down-regulation in SHR carotid arteries. The present study thus provides additional insights into the vascular beneficial effects of berberine in hypertension.
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Peking, China. Electronic address: liu_limei@126.com.
authors: Limei
authors: L
authors: Liu
authors: Institute of Vascular Medicine and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors: Jian
authors: J
authors: Liu
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Peking, China.
authors: Zhengxiang
authors: Z
authors: Huang
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Peking, China.
authors: Xiaoxing
authors: X
authors: Yu
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Peking, China.
authors: Xinyu
authors: X
authors: Zhang
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Peking, China.
authors: Dou
authors: D
authors: Dou
authors: Institute of Vascular Medicine and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China. Electronic address: yu-huang@cuhk.edu.hk.
authors: Yu
authors: Y
authors: Huang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D001599:Berberine; D051546:Cyclooxygenase 2; D055372:AMP-Activated Protein Kinases
keywords: Carotid artery; Cyclooxygenase; Endoplasmic reticulum stress; Endothelial function; Spontaneously hypertensive rats