Angiotensin type 2 receptors in the intermediolateral cell column of the spinal cord: Negative regulation of sympathetic nerve activity and blood pressure

Background: Our previous study demonstrated that AT2R in brainstem nuclei participated in the regulation of sympathetic outflow and cardiovascular function. However, the functional significance of AT2R in the intermediolateral cell column (IML) of the thoracic spinal cord in normal rats remains elusive. We hypothesized that AT2R activation in the IML exerts a sympatho-inhibitory effect. Methods and results: UsingWestern-blot analysis, immunohistochemical staining and quantitative real-time PCR, both AT1R and AT2R expressions were detected in the spinal cord. The highest AT2R protein expression was found in the IML, while AT1R expression didn't display regional differenceswithin the graymatter. Microinjection of Ang II into the IML dose-dependently elevated mean blood pressure (MAP, employing a transducer-tipped catheter) and renal sympathetic nerve activity (RSNA, using a pair of platinum-iridium recording electrodes), which were completely abolished by Losartan, and attenuated by TEMPOL and apocynin. Activation of AT2R in the IML with CGP42112 evoked hypotension (.MAP: -21 +/- 4 mm Hg) and sympatho-inhibition (RSNA: 73 +/- 3% of baseline), which were completely abolished by PD123319 and L-NAME. Blockade of AT2R in the IML with PD123319 significantly increased MAP (11 +/- 1 mm Hg) and sympathetic nerve activity (RSNA: 133 +/- 13% of baseline). Moreover, PD123319 significantly enhanced the Ang II induced pressor response. Furthermore, in isolated IML neurons, CGP42112 treatment augmented potassium current and decreased resting membrane potential by employing whole-cell patch clamp. Conclusion: In the normal condition, AT2R in the IML tonically inhibits sympathetic activity through an NO/NOS dependent pathway and subsequent potassium channel activation. (C) 2013 Elsevier Ireland Ltd. All rights reserved.