title: Notoginsenoside R1 attenuates hypoxia and hypercapnia-induced vasoconstriction in isolated rat pulmonary arterial rings by reducing the expression of ERK.
abstract: Pulmonary arterial hypertension (PAH) is a disease of the small pulmonary arteries characterized by increased vascular resistance. Pulmonary vasoconstriction has been proven to play a pivotal role in PAH. We have previously hypothesized that Panax notoginseng saponins (PNS) might attenuate hypoxia-hypercapnia-induced pulmonary vasoconstriction. The specific objective of the present study was to investigate the role of notoginsenoside R1, a main ingredient of PNS, in this process and the possible underlying mechanism. The third order pulmonary rings from the Sprague-Dawley rats were treated with different concentrations of notoginsenoside R1 (8, 40, and 100 mg/L, respectively) both before and during the conditions of hypercapnia and hypoxia. Contractile force changes in the rings were detected and the optimal concentration (8 mg/L) was selected. Furthermore, an ERK inhibitor, U0126, was applied to the rings. In addition, pulmonary arterial smooth muscle cells (PASMCs) were cultured under hypoxic and hypercapnic conditions, and notoginsenoside R1 was administered to detect the changes induced by ERK1/2. The results revealed biphasic vasoconstriction in rings under hypoxic and hypercapnic conditions. It is hypothesized that the observed attenuation of vasoconstriction and the production of vasodilation could have been induced by notoginsenoside R1. This effect was found to be significantly reinforced by U0126 (p < 0.05 or p < 0.01). ERK expression in the PASMCs under hypoxic and hypercapnic conditions was significantly activated (p < 0.05 or p < 0.01) and the observed activation was attenuated by notoginsenoside R1 (p < 0.05 or p < 0.01). Our findings strongly support the significant role of notoginsenoside R1 in the inhibition of hypoxia-hypercapnia-induced vasoconstriction by the ERK pathway.
authors.affiliation: Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China , Wenzhou Medical University Renji College, Wenzhou, Zhejiang 325035, China.
authors.forename: Yixiao
authors.initials: Y
authors.lastname: Xu
authors.forename: Lina
authors.initials: L
authors.lastname: Lin
authors.forename: Lanlan
authors.initials: L
authors.lastname: Tang
authors.forename: Mengxiao
authors.initials: M
authors.lastname: Zheng
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Ma
authors.forename: Linjing
authors.initials: L
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Meng
authors.forename: Wantie
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism* / Q000502:physiology; D036145:Ginsenosides / Q000494:pharmacology*; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D053723:Panax notoginseng; D011651:Pulmonary Artery / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D036145:Ginsenosides; D048049:Extracellular Signal-Regulated MAP Kinases; C072936:notoginsenoside R1
keywords: ERK; Hypercapnia; Hypoxia; Notoginsenoside R1; Pulmonary Hypertension