title: Modulation of angiotensin II responses in sympathetic neurons by cytosolic calcium.
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.
authors.affiliation: Department of Pharmacology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA.
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Fernandez
authors.forename: Ming-He
authors.initials: MH
authors.lastname: Huang
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Davidson
authors.forename: Paul R
authors.initials: PR
authors.lastname: Knight
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Izzo
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D017136:Ion Transport; D007700:Kinetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D013233:Stellate Ganglion / Q000187:drug effects / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000166:cytology / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D015544:Inositol 1,4,5-Trisphosphate; D012964:Sodium; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine