title: Rostral ventrolateral medulla opioid receptor activation modulates glutamate release and attenuates the exercise pressor reflex.
abstract: We previously reported that the administration of [D-Ala(2)]methionine enkephalinamide (DAME), an opioid receptor agonist, into the rostral (RVLM) but not into the caudal ventrolateral medulla (CVLM), attenuated increases in mean arterial pressure (MAP) and heart rate (HR) during static muscle contraction that had been blocked by prior microdialysis of the opioid receptor antagonist, naloxone [Am. J. Physiol. 274 (1998) H139-H146]. In this study, we determine whether this RVLM-mediated opioidergic-modulation of cardiovascular responses is associated with localized changes in extracellular concentrations of glutamate, an excitatory amino acid, using microdialysis techniques in anesthetized rats. Muscle contraction increased MAP and HR by 37+/-5 mmHg and 23+/-3 bpm, respectively. Extracellular glutamate concentrations, determined using HPLC-ECD, increased from 0.8+/-0.2 to 6.6+/-1.2 ng/5 microliter in the bilateral RVLM areas. Microdialysis of DAME (100 microM) for 30 min attenuated the contraction-evoked increases in MAP, HR, and glutamate levels (20+/-4 mmHg, 10+/-2 bpm, and 1.8+/-0.2 ng/5 microliter, respectively). After microdialysis of naloxone (100 microM) for 30 min into the RVLM, muscle contraction blocked the attenuations (35+/-5 mmHg, 26+/-4 bpm, and 5.8+/-1.0 ng/5 microliter, respectively). Developed muscle tensions were similar throughout the protocol (676+/-38, 678+/-37 and 687+/-37 g, respectively). These results suggest that an opioidergic receptor-mediated mechanism within the RVLM attenuates cardiovascular responses during static exercise via modulating extracellular concentrations of glutamate in the RVLM.
authors.affiliation: Third Department of Internal Medicine, Chiba University School of Medicine, 260, Chiba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ishide
authors.forename: M
authors.initials: M
authors.lastname: Mancini
authors.forename: T J
authors.initials: TJ
authors.lastname: Maher
authors.forename: P
authors.initials: P
authors.lastname: Chayaikul
authors.forename: A
authors.initials: A
authors.lastname: Ally
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*
chemical_list: D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone; D018698:Glutamic Acid; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-