Notoginsenoside R1 Attenuates Hypoxia and Hypercapnia-Induced Vasoconstriction in Isolated Rat Pulmonary Arterial Rings by Reducing the Expression of ERK

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 R-1, 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 R-1 (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 R-1 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 R-1. 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 R-1 (p < 0: 05 or p < 0: 01). Our findings strongly support the significant role of notoginsenoside R-1 in the inhibition of hypoxia-hypercapnia- induced vasoconstriction by the ERK pathway.