title: Angiotensin II type-2 (AT2) receptor antagonism alters cardiovascular responses to static exercise and simultaneously changes glutamate/GABA levels within the ventrolateral medulla.
abstract: Angiotensin II receptors (Ang II), classified into AT1 and AT2 subtypes, are located in different regions of the central nervous system, including the cardiovascular control centers in the medulla oblongata. We previously reported the role of Ang II AT1 receptors within the medulla on cardiovascular responses and glutamate/GABA neurotransmission during the exercise pressor reflex [Patel, D., Böhlke, M., Phattanarudee, S., Kabadi, S., Maher, T.J., Ally, A., 2008. Cardiovascular responses and neurotransmitter changes during blockade of angiotensin II receptors within the ventrolateral medulla. Neurosci. Res. 60 (3), 340-348]. In this study, we investigated the role of the AT2 receptor subtype within the ventrolateral medullary region (VLM) in modulating increases in mean arterial pressure (MAP) and heart rate (HR) in response to static skeletal muscle contraction.
  
  
  METHODS
  Using microdialysis methods in anesthetized rats, we administered AR-AT2 antagonists into the rostral (RVLM) and caudal (CVLM) VLM and determined its effects on cardiovascular responses and glutamate/GABA neurotransmission following muscle contraction. Bilateral microdialysis of a selective AT2 antagonist, PD 123319 (10 microM), for 30 min into the RVLM augmented MAP and HR responses during a static muscle contraction. Simultaneously, the drug increased glutamate and decreased GABA levels within the RVLM. After 60 min of discontinuation of the drug, only MAP and HR values but not the neurotransmitter levels in response to a muscle contraction returned to baseline. In contrast, bilateral microdialysis of the drug into the CVLM attenuated cardiovascular responses during a static muscle contraction, decreased glutamate and increased GABA. However, only the cardiovascular responses recovered after 60 min of discontinuation of the drug. These results demonstrate that AT2 within both RVLM and CVLM plays important differential roles in modulating neurotransmission and cardiovascular function during the exercise pressor reflex.
authors.affiliation: Department of Pharmaceutical Sciences, Massachusetts College of Pharmacy and Health Sciences, 179 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Tedesco
authors.forename: Ahmmed
authors.initials: A
authors.lastname: Ally
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D045604:Extracellular Fluid / Q000737:chemistry / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D017551:Microdialysis; D009119:Muscle Contraction / Q000502:physiology; D010805:Physical Conditioning, Animal; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012154:Reticular Formation / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid