Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats

Abstract

Objectives: To examine the protective effect of Rhynchophylline (Rhy) on vascular endothelial function in spontaneous hypertensive rats (SHRs) and the underlying mechanism.Methods: Intrarenal arteries of SHRs and Wistar rats were suspended in myograph for force measurement. Expression and phosphorylation of endothelial nitric oxide (NO) synthase (eNOS), Akt, and Src kinase (Src) were examined by Western blotting. NO production was assayed by ELISA.Results: Rhy time- and concentration-dependently improved endothelium-dependent relaxation in the renal arteries from SHRs, but had no effect on endothelium-independent relaxation in SHR renal arteries. Wortmannin (an inhibitor of phosphatidylinositol 3-kinase) or PP2 (an inhibitor of Src) inhibited the improvement of relaxation in response to acetylcholine by 12 h-incubation with 300 μM Rhy. Western blot analysis revealed that Rhy elevated phosphorylations of eNOS, Akt, and Src in SHR renal arteries. Moreover, wortmannin reversed the increased phosphorylations of Akt and eNOS induced by Rhy, but did not affect the phosphorylation of Src. Furthermore, the enhanced phosphorylations of eNOS, Akt, and Src were blunted by PP2. Importantly, Rhy increased NO production and this effect was blocked by inhibition of Src or PI3K/Akt.Conclusion: The present study provides evidences for the first time that Rhy ameliorates endothelial dysfunction in SHRs through the activation of Src-PI3K/Akt-eNOS signaling pathway.

The cyclooxygenase-1/mPGES-1/endothelial prostaglandin EP4 receptor pathway constrains myocardial ischemia-reperfusion injury

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Editorial: Traditional Chinese Medicine: Organ Vascular Injury - Volume II

“…There was also reduced Evans blue extravasation and cerebral edema, upregulation of ATPα and ATP5D, the two subunits of mitochondrial complex V, in extracted protein from brain tissue, elevation of the ratio of ATP/ADP and ATP/AMP, and inhibition of the damage of hippocampal neurons (Jiao et al). Hao et al from the team of professor Jing-Yan Han also demonstrated that Rhynchophylline, one of the main components of YangXue QingNao Wan, was capable of activating Src-PI3K/Akt-eNOS cascade and improving endothelium-dependent relaxation in the renal arteries from SHRs (Hao et al, 2017). Song et al from the team of Professors Huayun Yu and Zhichun Wu demonstrated that Zi Shen Huo Luo formula could enhance the efficacy of angiotensinconverting enzyme inhibitors in left ventricular hypertrophy after hypertension by improving aldosterone activity and affecting mineralocorticoid receptor and Caveolin-1 colocalization and the downstream EGFR signaling pathway.…”