Angiotensin II and glutamate influence area postrema neurons in rat brain slices.
The area postrema (AP) has been repeatedly implicated in cardiovascular regulation. Microinjection and single unit recording studies in vivo have suggested specific actions for angiotensin II (ANG) and glutamate (GLU) in controlling the excitability of AP neurons. The present study was therefore designed to examine the responsiveness of AP neurons to bath administration of these substances. Of the 133 AP neurons tested with ANG (10(-8)-10(-6) M) 40% were excited, 13% inhibited and the remainder unresponsive. The excitatory effects of ANG on AP neurons were dose-dependent. Following blockade of synaptic transmission with a low calcium high magnesium solution excitatory responses were maintained in 12 of 15 cells tested. Pretreatment of slices with the AT1 receptor antagonist losartan blocked the excitatory effects of ANG in all cells (5/5) tested. The effects of GLU on AP neurons were also examined. Of the 71 AP cells tested, 40% were excited, 10% inhibited, 8% showed excitatory responses followed by periods of inhibition while the remaining cells were unaffected. Excitatory effects of GLU were maintained in all AP neurons (7/7) tested during perfusion with low calcium, high magnesium solutions. Similar responses to NMDA were observed in four of four cells tested, suggesting these GLU actions are mediated through NMDA receptors. These data demonstrate direct excitatory actions of ANG and GLU on AP neurons which are likely mediated through the AT1 and NMDA receptors, respectively.
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Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Ferguson
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D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000737:chemistry; D004594:Electrophysiology; D018846:Excitatory Amino Acids; D018698:Glutamic Acid / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001713:Biphenyl Compounds; D018846:Excitatory Amino Acids; D007093:Imidazoles; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D018698:Glutamic Acid; D019808:Losartan