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(Circulation Research. 2001;88:787.)
© 2001 American Heart Association, Inc.

Cellular Biology

Angiotensin Selectively Activates a Subpopulation of Postganglionic Sympathetic Neurons in Mice

Xiuying Ma, Mark W. Chapleau, Carol A. Whiteis, Francois M. Abboud, Klaus Bielefeldt

From the Departments of Internal Medicine (X.Y.M., M.W.C., C.A.W., F.M.A., K.B.) and Physiology and Biophysics (F.M.A.), The Cardiovascular Center, University of Iowa College of Medicine, and the Department of Veterans Affairs Medical Center (M.W.C.), Iowa City, Iowa.

Correspondence to Xiuying Ma, MD, PhD, Department of Internal Medicine, 602 MRC, University of Iowa College of Medicine, Iowa City, IA 52242. E-mail xiuying-ma{at}uiowa.edu

Abstract—Angiotensin II (Ang II) increases renal sympathetic nerve activity in anesthetized mice before and after ganglionic blockade, suggesting that Ang II may directly activate postganglionic sympathetic neurons. The present study directly tested this hypothesis in vitro. Neurons were dissociated from aortic-renal and celiac ganglia of C57BL/6J mice. Cytosolic Ca²⁺ concentration ([Ca²⁺]ⁱ) was measured with ratio imaging using fura 2. Ang II increased [Ca²⁺]ⁱ in a subpopulation of sympathetic neurons. At a concentration of 200 nmol/L, 14 (67%) of 21 neurons responded with a rise in [Ca²⁺]ⁱ. The Ang II type 1 (AT¹) receptor blocker (losartan, 2 µmol/L) but not the Ang II type 2 (AT²) receptor blocker (PD123,319, 4 µmol/L) blocked this effect. The Ang II–induced [Ca²⁺]ⁱ increase was abolished by removal of extracellular Ca²⁺ but not altered by depletion of intracellular Ca²⁺ stores with thapsigargin. Ang II no longer elicited a [Ca²⁺]ⁱ increase in the presence of lanthanum (25 µmol/L). The specific N-type and L-type Ca²⁺ channel blockers, -conotoxin GVIA and nifedipine, respectively, significantly inhibited the Ang II–induced [Ca²⁺]ⁱ increase. The protein kinase C inhibitor H7 but not the protein kinase A inhibitor H89 blocked the response to Ang II. These results demonstrate that Ang II selectively activates a subpopulation of postganglionic sympathetic neurons in aortic-renal and celiac ganglia, triggering Ca²⁺ influx through voltage-gated Ca²⁺ channels. This effect is mediated through AT¹ receptors and requires the activation of protein kinase C. The activation of a subgroup of sympathetic neurons by Ang II may exert unique effects on kidney function in pathological states associated with elevated Ang II.

Key Words: calcium imaging • calcium influx • calcium channel blockers • protein kinase activation

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