Salidroside ameliorates hypoxic pulmonary hypertension by regulating the two-pore domain potassium TASK-1 channel.

Background: Hypoxic pulmonary vasoconstriction (HPV) is a reflex constriction of vascular smooth muscle. This study aims to investigate the role of Salidroside (Sal) in pulmonary arterial dilatation and the potential mechanism of Sal regulating hypoxic pulmonary hypertension in vitro and in vivo.
Methods: A rat model of hypoxic pulmonary hypertension (HPH) was constructed using hypoxic chamber. The effect of Sal on HPH were evaluated using vascular ring, whole cell patch-clamp, WGA staining, HE staining, and Sirius Scarlet staining assays.
Results: Sal treatment alleviated the injury of acute hypoxia on pulmonary circulation in SD rats. Meanwhile, Sal treatment reduced the pulmonary vascular tone of acute hypoxia in a concentration-dependent manner, which was involved in the TWIK-related acid-sensitive potassium channel 1 (TASK-1) mediating diastolic effect. We found that Sal treatment significantly increased the TASK-1 current of pulmonary artery smooth muscle cells (PASMCs) in a concentration-dependent manner, as well as reversed the inhibitory effect of acute hypoxia on the TASK-1 current. Moreover, Sal treatment improved the TASK-1 current density, suppressed the proliferation, and enhanced the apoptosis of PASMCs in SD rats under continuous hypoxic condition. In addition, we found that the electrophysiological remodeling and pulmonary vascular remodeling of PASMCs were improved by the treatment of Sal through the regulation of TASK-1 channel.
Conclusions: Sal could alleviate HPH by restoring the function of TASK-1 channel, which may provide a novel method for the treatment of HPH.
Competing Interests: Declaration of competing interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.
(Copyright © 2024. Published by Elsevier GmbH.)