Altered mitochondrial dynamics contributes to endothelial dysfunction in hypertension

Aims Impaired mitochondrial dynamics is implicated in cardiovascular diseases. Alterations in mitochondrial dynamics and reactive oxygen species production have been shown to be associated with the development of hypertension. However, the role of mitochondrial dynamics in endothelial dysfunction during the development of hypertension remains unknown. Methods Effects of mitochondrial fission inhibitor mdivi‐1 on vascular contraction and relaxation were examined on mesenteric arteries isolated from WKY or SHR rats. Mitochondrial networks in aortic endothelia were assessed using transmission electron microscope, and further evaluated with laser confocal after labeling with 100 nmol/L MitoTracker Green FM. In vitro, effects of Angiotensin□(10 −6 M, 24 h) on mitochondrial morphology in HUVECs were investigated. Results Pretreatment with mdivi‐1 inhibited PE‐induced mesenteric artery constriction in WKY rats, and the inhibitory effect of mdivi‐1 was attenuated on endothelium‐denuded mesenteric arteries. Then we observed mitochondrial fragmentation, increased mitochondrial reactive oxygen species production and increased expression of dynamin‐related protein 1 (Drp1) in aortic endothelial cells from SHR rats. Mdivi‐1 pretreatment ameliorated acetylcholine induced mesenteric artery relaxation in SHR rats. In cultured HUVECs exposed to Angiotensin□, we observed a similar loss of mitochondrial networks and increased expression of Drp1. Altered mitochondrial dynamics was associated with increased mitochondrial reactive oxygen species production and a marked impairment of insulin‐stimulated activation of endothelial nitric oxide synthase and endothelial autophagy. Silencing Drp1 with siRNA blunted Angiotensin□induced alterations in mitochondrial networks, reactive oxygen species production, endothelial nitric oxide synthase activation and endothelial autophagy. Conclusions These findings show that up‐regulation of Drp1 during hypertension exacerbates endothelial dysfunction by increasing mitochondrial reactive oxygen species and subsequently inhibiting endothelial nitric oxide synthase activation and autophagy. Support or Funding Information This study was supported by the grants from the National Natural Science Foundation of China (Grant Nos. AWS16J018, 81670253) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .