title: Dlitiazem inhibits the oxidative stress induced by angiotensin II through growth hormone secretagogue receptor type 1a in human umbilicus vein endothelial cells.
abstract: Diltiazem has been used for post-transplant hypertension, but the mechanism underlying its protective effect of endothelial cells against angiotensin II (Ang II) - induced impairment remains unclear. Human umbilicus vein endothelial cells (HUVECs) were cultured and divided into seven groups: control, Ang II (10-6M), diltiazem (10-6M), [D-Lys3]-GHRP-6(25μM), diltiazem (10-6M)+Ang II (10-6M), losartan (10-6M)+Ang II (10-6M), [D-Lys3]-GHRP-6 (25μM) + Dil(10-6M)+Ang II (10-6M) groups. Nitric oxide (NO) production, intracellular reactive oxygen species (ROS) levels, protein and mRNA expressions of endothelial nitric oxide synthase (eNOS) and p47 phox subunit of NADPH were evaluated. Results indicated that pre- treatment with diltiazem significantly decreased the intracellular ROS levels and increased NO production. Treatment with 10-6M Ang II for 24h induced a significant decrease in the mRNA and protein levels of eNOS, which was significantly increased by the pre-incubated with diltiazem (10-6M). Treatment with 10-6M Ang II for 24h induced a significant increase in the mRNA and protein levels of p47 phox subunit of NADHP oxidase, which was significantly decreased by the pre-incubated with diltiazem. However, all of these protective roles of diltiazem were attenuated by pre-incubation of [D-Lys3]-GHRP-6. The results reveal that diltiazem inhibits the Ang II - induced oxidative stress in HUVECs, which may be partly mediated by GHSR1a.
authors.affiliation: Clinical Pharmacy and Pharmacology Research Institute, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Clinical Pharmacy and Pharmacology Research Institute, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.affiliation: Clinical Pharmacy and Pharmacology Research Institute, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Shanru
authors.initials: S
authors.lastname: Zuo
authors.affiliation: Clinical Pharmacy and Pharmacology Research Institute, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Guan
authors.affiliation: Clinical Pharmacy and Pharmacology Research Institute, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Jianglin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Clinical Pharmacy and Pharmacology Research Institute, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Clinical Pharmacy and Pharmacology Research Institute, Third Xiangya Hospital, Central South University, Changsha 410013, China. Electronic address: zuoxc08@126.com.
authors.forename: Xiaocong
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Clinical Pharmacy and Pharmacology Research Institute, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Sujie
authors.initials: S
authors.lastname: Jia
authors.affiliation: Clinical Pharmacy and Pharmacology Research Institute, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Guo
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C000626362:Ghsr1a protein, human; D017382:Reactive Oxygen Species; D054440:Receptors, Ghrelin; D014665:Vasodilator Agents; D000804:Angiotensin II; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D004110:Diltiazem
keywords: Diltiazem; GHSR1a; HUVECs; Oxidative stress