Key result
AFNP reduces hypertension and aortic remodeling in rats by inhibiting the RhoA/ROCK pathway.
Why the study?
The protective role of alkaloids from Nelumbinis Plumula (AFNP) on the aorta during hypertension is not yet fully understood.
Does AFNP ameliorate aortic remodeling and hypertension via the RhoA/ROCK pathway in preclinical models?
Does AFNP ameliorate aortic remodeling and hypertension via the RhoA/ROCK pathway in preclinical models?
AFNP exerts anti-hypertensive and aortic protective effects by inhibiting VSMC cytoskeleton remodeling via the RhoA/ROCK pathway.
Should not yet change hypertension management; leaves open translation of AFNP effects to human aortic remodeling.
The protective role of alkaloids from Nelumbinis Plumula (AFNP) on the aorta during hypertension is not yet fully understood. We hypothesize that AFNP exerts protective effects against Ang II-induced hypertension by mediating RhoA/ROCK pathway and phenotypic switching during hypertension. In the present study, we evaluated the effect of AFNP on angiotensin II (Ang II)-induced actin cytoskeleton reorganization and aorta remodeling, as well as the involvement of RhoA/Rho-associated coiled kinase (ROCK) pathway in protecting against hypertension. We used rat aortic tissues to investigate the vasodilatation effect of AFNP on Ang II-induced constriction. AFNP was shown to significantly relax the endothelium-intact arteries induced by Ang II. We further investigated the vasodilation effect of AFNP in endothelium denuded arteries, which showed that the action of AFNP was endothelial independent. Male SHR rats were treated with saline or AFNP and morphological changes were examined following 8 weeks. AFNP treatment normalized the effects of hypertension in SHRs. HE staining showed that AFNP treatment improved the tunica media and wall thickness and ratio of MT/LD and MA/LA. Western blotting showed that AFNP treatment markedly decreased the Ang II-induced expression of collagen I and increased α-SMA in aorta. Furthermore, MTT assay showed that AFNP inhibited the proliferation of Ang II treated VSMCs in a concentration-dependent manner. AFNP treatment also ameliorated F-actin cytoskeleton remodeling in Ang II treated VSMCs, as visualized under fluorescence microscopy. Western blot analysis showed that RhoA transposition and ROCK activation and phosphorylation of MYPT1 was increased following Ang II treatment but were inhibited by AFNP treatment, showing that the cardio-protective effect of AFNP is likely mediated by the RhoA/ROCK signaling pathway. The anti-hypertension and aortic protection effects of AFNP are due to non-endothelial dependent inhibition of the VSMC cytoskeleton remodeling and regulation of RhoA/ROCK pathway.
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Li et al. (2019) studied Hypertension. Alkaloids from Nelumbinis Plumula (AFNP) vs. Saline was evaluated on Morphological changes in aorta (tunica media, wall thickness, MT/LD, MA/LA). Alkaloids from Nelumbinis Plumula (AFNP) ameliorated hypertension and aortic remodeling in male SHR rats by inhibiting VSMC cytoskeleton remodeling via the RhoA/ROCK pathway.
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