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Abstract: FR-PO336

Piezo1 Mediates Vasodilation Induced by Acute Hyperglycemia in Mouse Renal Arteries and Microvessels

Session Information

Category: Diabetic Kidney Disease

  • 701 Diabetic Kidney Disease: Basic

Authors

  • Fei, Lingyan, Sun Yat-Sen University, Shenzhen, China
  • Zheng, Zhihua, Sun Yat-Sen University, Shenzhen, China
  • Jiang, Shan, Sun Yat-Sen University, Shenzhen, China
Background

Acute hyperglycemia (HG) is a risk factor for developing acute kidney injury and poor renal outcome in critically ill patients. The role of renal vasculature in this context is not clear. We hypothesize that HG-associated hyperosmolarity facilitates vasodilation through Piezo1-mediated eNOS activation.

Methods

Vasoreactivity of isolated mouse mesenteric (MA) and renal interlobar (ILA) arteries was analyzed using wire myography and that of renal afferent (AA) and efferent (EA) arterioles, and vasa recta (VR) using microvascular perfusion. Immunofluorescence and western blot were used for molecular analyses of isolated mouse blood vessels as well HUVECs.

Results

Pre-treatment with HG (44 mmol L-1 glucose; 4 h) increased acetylcholine (ACh)-induced relaxation in ILA and MA, which was prevented by eNOS inhibition using L-NAME. Hyperosmotic mannitol solution had a similar effect. HG induced an immediate, L-NAME-inhibitable dilation in AA, EA, and VR, whereby stronger dilation in AA compared to EA. HG also increased glomerular filtration rate in mice. In HUVECs, HG and the Piezo1 activator Yoda1 increased levels of Piezo1 protein, phosphorylated CaMKII (p-CaMKII), Akt, and p-eNOS. The HG-effect could be prevented by inhibiting Piezo1 using GsMTx4 and CaMKII using KN93. Furthermore, in arteries and microvessels, inhibition of Piezo1 using GsMTx4 prevented the HG-effect, while Yoda1 caused relaxation and dilation, respectively.

Conclusion

Results reveal that Piezo1 mediates renal vasodilation induced by hyperosmolarity in acute HG. This mechanism may contribute to the pathogenesis of renal damage by acute HG.

Funding

  • Government Support – Non-U.S.