Angiotensin selectively activates a subpopulation of postganglionic sympathetic neurons in mice

被引:27
作者
Ma, XY
Chapleau, MW
Whiteis, CA
Abboud, FM
Bielefeldt, K
机构
[1] Univ Iowa, Coll Med, Ctr Cardiovasc, Dept Internal Med, Iowa City, IA 52242 USA
[2] Univ Iowa, Coll Med, Ctr Cardiovasc, Dept Physiol & Biophys, Iowa City, IA 52242 USA
[3] Dept Vet Affairs Med Ctr, Iowa City, IA 52242 USA
关键词
calcium imaging; calcium influx; calcium channel blockers; protein kinase activation;
D O I
10.1161/hh0801.089542
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (AT(1)) receptor blocker (losartan, 2 mu mol/L) but not the Ang II type 2 (AT(2)) receptor blocker (PD123,319, 4 mu mol/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 mu mol/L). The specific N-type and L-type Ca2+ channel blockers, omega -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 AT. 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.
引用
收藏
页码:787 / 793
页数:7
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