title: Further evidence that extracellular serotonin in the rostral ventrolateral medulla modulates 5-HT(1A) receptor-mediated attenuation of exercise pressor reflex.
abstract: We determined changes in extracellular levels of glutamate, serotonin (5-HT), norepinephrine (NE), and dopamine (DA) within rostral ventrolateral medulla (RVLM) during 5-HT(1A)-receptor stimulation-mediated inhibition of cardiovascular responses to static muscle contraction using anesthetized rats. In ten rats, muscle contraction significantly increased (P<0.01) mean arterial pressure (MAP) by 29+/-4 mm Hg, heart rate (HR) by 25+/-3 bpm, and glutamate levels by 4.5+/-0.8 ng/5 microl. Microdialysis of a 5-HT(1A) receptor agonist, 8-OH-DPAT (10 mM), into the RVLM for 30 min attenuated cardiovascular responses to muscle contraction and had no effect on glutamate levels. A subsequent administration of 10 mM WAY100635, a 5-HT(1A) antagonist, into the RVLM antagonized the attenuating effects of 8-OH-DPAT. In another ten rats, muscle contraction significantly increased (P<0.01) MAP and HR by 20+/-2 mmHg and 25+/-8 bpm, respectively. In addition, levels of 5-HT, NE, and DA in the RVLM significantly increased (P<0.01) by 3.6+/-0.3, 3.2+/-0.3, and 3.3+/-0.4 pg/10 microl, respectively. Administration of 8-OH-DPAT (10 mM) into the RVLM for 30 min attenuated cardiovascular responses to muscle contraction and had no effects on NE and DA levels. However, the drug significantly attenuated 5-HT levels following a muscle contraction. Microdialysis of 10 mM WAY100635 into the RVLM reversed both cardiovascular and 5-HT changes. These results suggest that stimulation of 5-HT(1A)-receptors within the RVLM attenuates cardiovascular responses to static exercise via a reduction of extracellular 5-HT concentration and most likely not through changes in glutamate, NE or DA levels.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 10330, Bangkok, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Chaiyakul
authors.forename: D
authors.initials: D
authors.lastname: Reidman
authors.forename: L
authors.initials: L
authors.lastname: Pilipovic
authors.forename: T
authors.initials: T
authors.lastname: Maher
authors.forename: A
authors.initials: A
authors.lastname: Ally
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena; D004298:Dopamine / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D009043:Motor Activity / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*
chemical_list: D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D018698:Glutamic Acid; D004298:Dopamine; D009638:Norepinephrine