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

• Published in: International journal of cardiology Vol. 168; no. 4; pp. 4046 - 4055
• Main Authors: Chao, Jie, Gao, Juan, Parbhu, Karma-Jaya K, Gao, Lie
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 09.10.2013; Elsevier
• Subjects: Adrenergic Fibers - drug effects; Adrenergic Fibers - physiology; Angiotensin II - pharmacology; Angiotensin II Type 2 Receptor Blockers - pharmacology; Angiotensin type 1 receptor; Angiotensin type 2 receptor; Animals; Arterial blood pressure; Biological and medical sciences; Blood Pressure - drug effects; Blood Pressure - physiology; Cardiology. Vascular system; Cardiovascular; Heart; Imidazoles - pharmacology; Intermediolateral cell column; Male; Medical sciences; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 2 - physiology; Renal sympathetic nerve activity; Spinal Cord - drug effects; Spinal Cord - physiology; Angiotensin type 1 receptor; Arterial blood pressure; Renal sympathetic nerve activity; Intermediolateral cell column; Angiotensin type 2 receptor; Sympathetic nerve; Spinal cord; Central nervous system; Activity; Cardiovascular disease; Arterial blood; Renin angiotensin system; Regulation(control); Type; Angiotensin; Arterial pressure; Blood pressure; Hemodynamics; Cardiology; Cell; Renal nerve; Biological receptor
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2013.06.051

Abstract 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 Using Western-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 differences within the gray matter. 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 (ΔMAP: − 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.