title: Ginsenoside Rg1 attenuates hypoxia and hypercapnia-induced vasoconstriction in isolated rat pulmonary arterial rings by reducing the expression of p38.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is a fatal disease characterized by increased pulmonary arteriolar resistance. Pulmonary vasoconstriction has been proved to play a significant role in PAH. We previously reported that Panax notoginseng saponins (PNS) might attenuate hypoxia and hypercapnia-induced pulmonary vasoconstriction (HHPV).
  
  
  METHODS
  In the present study, our specific objective was to investigate the role of ginsenoside Rg1, a major component of PNS, in this process and the possible underlying mechanism. The second order pulmonary rings isolated from the Sprague-Dawley rats were treated with different dosage of ginsenoside Rg1 at 8, 40, or 100 mg/L respectively, both before and during the conditions of hypoxia and hypercapnia. Contractile force changes of the rings were detected. Furthermore, SB203580, the selective inhibitor for p38 activation was applied to the rings. Pulmonary arterial smooth muscle cells (PASMCs) were cultured under hypoxic and hypercapnic conditions, and ginsenoside Rg1 was administered to detect the changes induced by p38.
  
  
  RESULTS
  Under the hypoxic and hypercapnic conditions, we observed a biphasic pulmonary artery contractile response to the second pulmonary artery rings. It is hypothesized that the observed attenuation of vasoconstriction and the production of vasodilation could have been induced by ginsenoside Rg1. This effect was significantly reinforced by SB203580 (P<0.05 or P<0.01). The expression of p38 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 ginsenoside Rg1 (P<0.05 or P<0.01).
  
  
  CONCLUSIONS
  Our findings strongly support the significant role of ginsenoside Rg1 in the inhibition of hypoxia and hypercapnia-induced vasoconstriction by the p38 pathway.
authors: Department of Pathophysiology, Wenzhou Medical University, Wenzhou 325035, China ;
authors: Mengxiao
authors: M
authors: Zheng
authors: Department of Pathophysiology, Wenzhou Medical University, Wenzhou 325035, China ;
authors: Meiping
authors: M
authors: Zhao
authors: Department of Pathophysiology, Wenzhou Medical University, Wenzhou 325035, China ;
authors: Lanlan
authors: L
authors: Tang
authors: Department of Pathophysiology, Wenzhou Medical University, Wenzhou 325035, China ;
authors: Congcong
authors: C
authors: Zhang
authors: Division of Cardiovascular Medicine University of Iowa Carver College of Medicine, Iowa City 52242, USA.
authors: Longsheng
authors: L
authors: Song
authors: Department of Pathophysiology, Wenzhou Medical University, Wenzhou 325035, China ;
authors: Wantie
authors: W
authors: Wang
keywords: Ginsenoside Rg1; hypercapnia; hypoxia; p38; pulmonary hypertension