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2017 ; 8
(ä): 928
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Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade
in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats
#MMPMID29187825
Hao HF
; Liu LM
; Pan CS
; Wang CS
; Gao YS
; Fan JY
; Han JY
Front Physiol
2017[]; 8
(ä): 928
PMID29187825
show ga
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 ?M 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.