A11798 Counter-regulation of autophagy by dopamine D1-like receptors and angiotensin II type 1 receptor in vascular smooth muscle cells

Abstract

Objectives: To investigate the interaction between dopaminergic and renin-angiotensin systems in vascular smooth muscle cells. Methods: Autophagic influx was determined in the presence of dopamine D1 like receptor and angiotensin type I receptor pharmacological reagents in vascular smooth muscle cells. Results: In A10 aortic vascular smooth muscle cells, fenoldopam, a D1-like receptor agonist, decreased angiotensin II type 1 receptor (AT1R) protein expression and increased the protein expressions of autophagy hallmark proteins, autophagy protein 5 (ATG5) and microtubule-associated protein 1 light chain (LC)3-II, effects that were blocked by Sch23390, D1-like receptor antagonist. By contrast, angiotensin II, the endogenous AT1R agonist, decreased the protein expression of the D5 dopamine receptor (D5R), one of the two D1-like receptors, and autophagy hallmark proteins, which were inhibited by losartan, an AT1R antagonist. Furthermore, Rp-cAMP (PKA inhibitor), but not rapamycin (mTOR inhibitor), abrogated the effects of fenoldopam on authophagy protein expression. By contrast, rapamycin but not Rp-cAMP, abrogated the effects of angiotensin II on autophagy and D5R protein expression. Angiotensin II also decreased the expression of D1R, the other D1-like dopamine receptor, but it was not through autophagy. Conclusion: These results demonstrate a counter regulation between D5R and AT1R through cAMP/PKA and mTOR signaling pathways, respectively, in vascular smooth muscle cells.