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Cardiovascular responses to hydrogen peroxide into the nucleus tractus solitarius

¹Department of Physiology, Federal University of São Paulo, São Paulo-SP, Brazil; ²Department of Physiology and Pathology, São Paulo State University, Araraquara-SP, Brazil; ³Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas; and ⁴Department of Biological Sciences, Federal University of Ouro Preto, Ouro Preto-MG, Brazil

Submitted 23 September 2008 ; accepted in final form 1 June 2009

The nucleus tractus solitarius (NTS), a major hindbrain area involved in cardiovascular regulation, receives primary afferent fibers from peripheral baroreceptors and chemoreceptors. Hydrogen peroxide (H₂O₂) is a relatively stable and diffusible reactive oxygen species (ROS), which acting centrally, may affect neural mechanisms. In the present study, we investigated effects of H₂O₂ alone or combined with the glutamatergic antagonist kynurenate into the NTS on mean arterial pressure (MAP) and heart rate (HR). Conscious or anesthetized (urethane and -chloralose) male Holtzman rats (280–320 g) were used. Injections of H₂O₂ (125 to 1500 pmol/40 nl) into the intermediate NTS of anesthetized rats evoked dose-dependent and transient hypotension (–18 ± 3 to –55 ± 11 mmHg) and bradycardia (–16 ± 5 to –116 ± 40 bpm). Injection of the catalase inhibitor 3-amino-1,2,4-triazole (100 nmol/40 nl) into the NTS also produced hypotension and bradycardia. Previous injection of the ionotropic L-glutamate receptor antagonist kynurenate (7 nmol/40 nl) attenuated by 48% the bradycardic response, without changing the hypotension evoked by H₂O₂ (500 pmol/40 nl) in anesthetized rats. The antioxidant L-ascorbate (600 pmol/80 nl) injected into the NTS attenuated the bradycardic (42%) and hypotensive (67%) responses to H₂O₂ (500 pmol/40 nl) into the NTS. In conscious rats, injection of H₂O₂ (50 nmol/100 nl) into the NTS also evoked intense bradycardia (–207 ± 8 bpm) and hypotension (–54 ± 6 mmHg) that were abolished by prior injection of kynurenate (7 nmol/100 nl). The results show that H₂O₂ into the NTS induces hypotension and bradycardia probably due to activation of glutamatergic mechanisms.

reactive oxygen species; catalase inhibition; kynurenic acid; blood pressure; heart rate