Gastrodin attenuates angiotensin II-induced vascular contraction and MLCK/p-MLC₂ pathway activation

Abstract

Context

Gastrodin has been used as antihypertension therapy in China; however, the mechanisms underlying the effects of gastrodin have yet to be fully elucidated.

Objective

To explore the therapeutic efficiency of gastrodin as an antihypertensive and determine the mechanisms underlying this effect.

Materials and methods

C57BL/6 mice were continuously administered angiotensin II (Ang II) (500 ng/kg/min) to induce hypertension. Mice were randomly divided into control, Ang II and Ang II + gastrodin groups. Mice received intragastric administration of gastrodin (5 mg/kg) or double distilled water once a day for 4 weeks. Blood pressure, pulse wave velocity (PWV), thickness of the abdominal aorta, pathological morphology and differential expression transcripts (DETs) were assessed. Abdominal aorta rings and primary isolated vascular smooth muscle cells were subjected to Ang II stimulation to induce hypertension as ex vivo and in vitro models, respectively. Vascular ring tension, release of Ca²⁺ and levels of proteins involved in the myosin light chain kinase (MLCK)/phospho-myosin light chain 2 (p-MLC₂) pathway were determined.

Results

Gastrodin treatment attenuated increases in blood pressure, PWV and thickness of the abdominal aorta. Treatment with gastrodin resulted in 2785 DETs and the enrichment of vascular contraction and calcium signalling pathways. Gastrodin treatment attenuated Ang II-induced vasoconstriction, produced a norepinephrine-precontracted vasodilation effect (attenuated by verapamil), and reduced intracellular Ca²⁺ release. Furthermore, gastrodin suppressed activation of the MLCK/p-MLC₂ pathway in vivo and in vitro.

Conclusions

Gastrodin treatment lowers blood pressure, suppresses Ang II-induced vascular contraction and MLCK/p-MLC₂ pathway activation, thereby demonstrating the mechanisms underlying the therapeutic efficacy of gastrodin as an antihypertensive.

Keywords:

• Hypertension
• vascular smooth muscle cells

Author contributions

QX and JP conceived and designed the experiments. ZG and XY conducted the animal experiments and analysis. ZG, XY and JL conducted H&E and IHC staining. ZG, MW and XZ conducted cell experiments and Western blotting. ZG, XY and YC analysed the data. ZG and AS drafted the manuscript. QX and JP provided material and revised the manuscript.

Disclosure statement

The authors have no conflicts of interest to declare.

Data availability statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This study was sponsored by the National Natural Science Foundation of China (U22A20372 and 82074363), the Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine (2021-QNRC2-B19), the Scientific Research Foundation for the Top Youth Talents of Fujian University of Traditional Chinese Medicine (XQB202202) and the Scientific Research Foundation for the High-level Talents, Fujian University of Traditional Chinese Medicine (X2020004-talents).