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A11776 Impaired regulation of autophagy by dopamine D1-like receptors in renal proximal tubule cells from spontaneously hypertensive rats

Objectives: To identify impairment of D1 like dopamine receptor mediated autophagy in spontaneously hypertensive rats. Methods: Autophagy hallmark protein expression and mitochondrial reactive oxygen species production were determined in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats. Results: In renal proximal tubule (RPT) cells from WKY rats, the D1-like receptor agonist fenoldopam decreased mitochondrial reactive oxygen species (mito-ROS) production and increased the protein expression of autophagy hallmark proteins, autophagy protein 5 (ATG5) and microtubule-associated protein 1 light chain (LC) 3-II, in a time dependent manner. In the presence of chloroquine, an autophagy inhibitor, fenoldopam further increased ATG5 and LC3-II expressions, effects that were blocked by Sch23390, a D1-like receptor antagonist. However, in renal proximal tubule cells from SHR, fenoldopam had no effect on the protein expression of autophagy hallmark proteins. Basal level of mito-ROS was markedly higher and protein expression of autophagy proteins was lower in RPT cells from SHR than those from WKY rats. There were no differences in the protein expression of pro-apoptotic protein Bax and anti-apoptotic protein Bcl-xL between these two strain rats. Similar results were observed in renal cortices from WKY and SHRs. Conclusion: We conclude that the impaired regulation of autophagy by dopamine D1-like receptors is associated with increased production of mito-ROS in the kidney of SHRs.