Published Online
on December 9, 2002

A more recent version of this article appeared on January 1, 2003

This Article Full Text (PDF) All Versions of this Article: 41/1/56    most recent 01.HYP.0000047513.75459.7Ev1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fernandez, S. F. Articles by Izzo, J. L. Search for Related Content PubMed PubMed Citation Articles by Fernandez, S. F. Articles by Izzo, J. L., Jr Related Collections Autonomic, reflex, and neurohumoral control of circulation

Submitted on June 18, 2002
Revised on July 25, 2002

Modulation of Angiotensin II Responses in Sympathetic Neurons by Cytosolic Calcium

Stanley F. Fernandez; Ming-He Huang; Bruce A. Davidson; Paul R. Knight III; and Joseph L. Izzo Jr^*

From the Departments of Pharmacology (S.F.F., J.L.I.), Medicine (J.L.I.), and Anesthesiology (B.A.D., P.R.K.), School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York; and University of Arizona Sarver Heart Center (M.-H.H.), Tuscon, Ariz.

^* To whom correspondence should be addressed. E-mail: JIzzo{at}KaleidaHealth.Org.

Abstract—Both stimulatory and suppressive responses of the sympathetic nervous system to angiotensin II (AII) have been reported in intact animals. To elucidate possible cellular mechanisms, we studied AII-induced changes in cytosolic Ca²⁺ ([Ca²⁺]i) in primary cultures of rat stellate ganglion neurons. Two different patterns of [Ca²⁺]i responses to AII were observed: dose-dependent increases in [Ca²⁺]i in cells with intrinsically low baseline [Ca²⁺]i (n=64) and dose-dependent suppression of [Ca²⁺]i in neurons with intrinsically higher baseline [Ca²⁺]i (n=46). Individual neurons could express both response patterns to AII. In neurons with low basal [Ca²⁺]i, superfusion with Ca²⁺ ionophore (ionomycin) increased [Ca²⁺]i and reversed the initial AII-induced stimulatory pattern. L-type Ca²⁺ channel antagonism (nifedipine) in neurons with high baseline [Ca²⁺]i lowered [Ca²⁺]i and reversed the initial AII-induced suppressive response. Both stimulatory and suppressive responses were abolished by AT₁ receptor antagonism (losartan). AII-induced stimulatory responses were blocked by IP₃ receptor antagonism (2-APB) and by thapsigargin. AII-induced suppression of neuronal [Ca²⁺]i was blunted when Na-Ca exchange was impaired. We conclude that [Ca²⁺]i acts as a switch for AII-mediated stimulatory and suppressive responses in individual sympathetic neurons. AT₁ receptor-mediated neuronal stimulation and suppression may allow local homeostatic adaptation to meet complex systemic needs.

Key words: sympathetic nervous system • angiotensin II • calcium • calcium channel blockers • norepinephrine • inositol

This article has been cited by other articles:

				A. G. Teschemacher, S. Wang, M. K. Raizada, J. F.R. Paton, and S. Kasparov Area-Specific Differences in Transmitter Release in Central Catecholaminergic Neurons of Spontaneously Hypertensive Rats Hypertension, August 1, 2008; 52(2): 351 - 358. [Abstract] [Full Text] [PDF]

				C. Y. Shim, J.-W. Ha, S. Park, E.-Y. Choi, D. Choi, S.-J. Rim, and N. Chung Exaggerated Blood Pressure Response to Exercise Is Associated With Augmented Rise of Angiotensin II During Exercise J. Am. Coll. Cardiol., July 22, 2008; 52(4): 287 - 292. [Abstract] [Full Text] [PDF]

				S. Wang, A. G. Teschemacher, J. F. R. Paton, and S. Kasparov Mechanism of nitric oxide action on inhibitory GABAergic signaling within the nucleus tractus solitarii FASEB J, July 1, 2006; 20(9): 1537 - 1539. [Abstract] [Full Text] [PDF]

				S. F. Fernandez, M.-H. Huang, B. A. Davidson, P. R Knight III, and J. L. Izzo Jr Mechanisms of Angiotensin II-Mediated Decreases in Intraneuronal Ca2+ in Calcium-Loaded Stellate Ganglion Neurons Hypertension, February 1, 2005; 45(2): 276 - 282. [Abstract] [Full Text] [PDF]