Angiotensin-(1–7) through Mas receptor up-regulates neuronal norepinephrine transporter via Akt and Erk1/2-dependent pathways (pages 46–55)
María A. Lopez Verrilli, Martín Rodriguez Fermepín, Nadia Longo Carbajosa, Silvina Landa, Bruno D. Cerrato, Silvia García, Belisario E. Fernandez and Mariela M. Gironacci
Article first published online: 24 NOV 2011 | DOI: 10.1111/j.1471-4159.2011.07552.x
Central NET upregulation by angiotensin-(1-7) in hypertension As angiotensin (Ang) (1–7) decreases norepinephrine (NE) content in the synaptic cleft, we investigated the effect of Ang-(1–7) on centrally NE neuronal uptake, the main mechanism for NE removal from the synaptic cleft, in hypothalamic neurons from hypertensive rats. We showed that Ang-(1–7) causes a long-term stimulatory effect on NE neuronal uptake by increasing NE transporter expression. This effect is coupled to Mas receptor activation acting through both MEK1/2-ERK1/2 and PI3-kinase/Akt-dependent pathways. In this way, Ang-(1–7) may regulate a pre-synaptic mechanism in maintaining appropriate synaptic NE levels during hypertensive conditions, thus contributing to the modulation of NE homeostasis and blood pressure regulation.