Kidney dopamine D 1 -like receptors and angiotensin 1–7 interaction inhibits renal Na + transporters

The role of dopamine D 1 -like receptors (DR) in the regulation of renal Na + transporters, natriuresis, and blood pressure is well established. However, the involvement of the angiotensin 1–7 (ANG 1−7)-Mas receptor in the regulation of Na + balance and blood pressure is not clear. The present study aimed to investigate the hypothesis that ANG 1–7 can regulate Na + homeostasis by modulating the renal dopamine system. Sprague-Dawley rats were infused with saline alone (vehicle) or saline with ANG 1–7, ANG 1–7 antagonist A-779, DR agonist SKF38393, and antagonist SCH23390. Infusion of ANG 1–7 caused significant natriuresis and diuresis compared with saline alone. Both natriuresis and diuresis were blocked by A-779 and SCH23390. SKF38393 caused a significant, SCH23390-sensitive natriuresis and diuresis, and A-779 had no effect on the SKF38393 response. Concomitant infusion of ANG 1–7 and SKF38393 did not show a cumulative effect compared with either agonist alone. Treatment of renal proximal tubules with ANG 1–7 or SKF38393 caused a significant decrease in Na + -K + -ATPase and Na + /H + exchanger isoform 3 activity. While SCH23390 blocked both ANG 1–7- and SKF38393-induced inhibition, the DR response was not sensitive to A-779. Additionally, ANG 1–7 activated PKG, enhanced tyrosine hydroxylase activity via Ser 40 phosphorylation, and increased renal dopamine production. These data suggest that ANG 1–7, via PKG, enhances tyrosine hydroxylase activity, which increases renal dopamine production and activation of DR and subsequent natriuresis. This study provides evidence for a unidirectional functional interaction between two G protein-coupled receptors to regulate renal Na + transporters and induce natriuresis.