title: Involvement of N-methyl-D-aspartate glutamate receptor and nitric oxide in cardiovascular responses to dynamic exercise in rats.
abstract: Dynamic exercise evokes sustained cardiovascular responses, which are characterized by arterial pressure and heart rate increases. Although it is well accepted that there is central nervous system mediation of cardiovascular adjustments during exercise, information on the role of neural pathways and signaling mechanisms is limited. It has been reported that glutamate, by acting on NMDA receptors, evokes the release of nitric oxide through activation of neuronal nitric oxide synthase (nNOS) in the brain. In the present study, we tested the hypothesis that NMDA receptors and nNOS are involved in cardiovascular responses evoked by an acute bout of exercise on a rodent treadmill. Moreover, we investigated possible central sites mediating control of responses to exercise through the NMDA receptor-nitric oxide pathway. Intraperitoneal administration of the selective NMDA glutamate receptor antagonist dizocilpine maleate (MK-801) reduced both the arterial pressure and heart rate increase evoked by dynamic exercise. Intraperitoneal treatment with the preferential nNOS inhibitor 7-nitroindazole reduced exercise-evoked tachycardiac response without affecting the pressor response. Moreover, treadmill running increased NO formation in the medial prefrontal cortex (MPFC), bed nucleus of the stria teminalis (BNST) and periaqueductal gray (PAG), and this effect was inhibited by systemic pretreatment with MK-801. Our findings demonstrate that NMDA receptors and nNOS mediate the tachycardiac response to dynamic exercise, possibly through an NMDA receptor-NO signaling mechanism. However, NMDA receptors, but not nNOS, mediate the exercise-evoked pressor response. The present results also provide evidence that MPFC, BNST and PAG may modulate physiological adjustments during dynamic exercise through NMDA receptor-NO signaling.
authors.affiliation: Laboratory of Pharmacology, Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University, UNESP, Araraquara, SP, 14801-902, Brazil.
authors.forename: Laura H A
authors.initials: LH
authors.lastname: Camargo
authors.forename: Fernando H F
authors.initials: FH
authors.lastname: Alves
authors.forename: Caroline
authors.initials: C
authors.lastname: Biojone
authors.forename: Fernando M A
authors.initials: FM
authors.lastname: Correa
authors.forename: Leonardo B M
authors.initials: LB
authors.lastname: Resstel
authors.forename: Carlos C
authors.initials: CC
authors.lastname: Crestani
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat