Altered nitroxidergic and NMDA receptor-mediated modulation of baroreflex-mediated heart rate in obese Zucker rats.
Arterial baroreflex, an important physiological regulatory system for buffering systemic blood pressure, is impaired in obesity. This study investigated whether the blunted baroreflex function in obesity is attributed to the altered nitroxidergic or N-methyl--aspartate (NMDA) mechanism. Baroreflex bradycardia responses, blood pressure and heart rate in 30 lean and 30 obese anesthetized Zucker rats (8-12 weeks of age) were assessed after injecting phenylephrine with intravenous preadministration of saline (control), dextromethorphan (DXM, NMDA receptor antagonist, 10 mg kg(-1)) or N(G)-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor, 100 mg kg(-1)). Compared with lean rats (-2.00+/-0.29 b.p.m. mm Hg(-1)), the baroreflex sensitivity (BRS) in obese rats (-0.43+/-0.05 b.p.m. mm Hg(-1)) was significantly blunted. The BRS was significantly suppressed by DXM in lean rats but not in obese rats. After administration of L-NAME, BRS was significantly suppressed in lean Zucker rats but not in obese Zucker rats. The normal BRS was significantly suppressed in lean rats after administration of both DXM and L-NAME, and the blunted BRS in obesity was significantly blocked to nearly no BRS after administration of both DXM and L-NAME. This study suggests that BRS is blunted in obese rats and that blunted baroreflex is, at least in part, attributed to altered nitroxidergic or NMDA receptor-mediated modulation.
Chen
Jwo-Sheng
JS
Department of Sports Medicine, China Medical University, Taichung, Taiwan.
Wang
Hui-Ju
HJ
Chang
Weng-Cheng
WC
Jao
Chin-Ci
CC
Wu
Bor-Tsang
BT
Shyu
Woei-Cherng
WC
Lee
Shin-Da
SD
D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003915:Dextromethorphan / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006339:Heart Rate / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D026602:Nitrergic Neurons / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D009765:Obesity / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013566:Sympathomimetics / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D013566:Sympathomimetics; D010656:Phenylephrine; D009569:Nitric Oxide; D003915:Dextromethorphan; D019331:NG-Nitroarginine Methyl Ester