Cardiovascular responses produced by central injection of hydrogen peroxide in conscious rats

Reactive oxygen species (ROS) have been shown to modulate neuronal synaptic transmission and may play a role on the autonomic control of the cardiovascular system. In this study we investigated the effects produced by hydrogen peroxide (H2O2) injected alone or combined with the anti-oxidant agent N-acetil-L-Cysteine (NAC) or catalase into the fourth brain ventricle (4th V) on mean arterial pressure and heart rate of conscious rats. Moreover the involvement of the autonomic nervous system on the cardiovascular responses to H2O2 into the 4th V was also investigated. Male Holtzman rats (280-320g) with a stainless steel cannula implanted into the 4th V and polyethylene carmulas inserted into the femoral artery and vein were used. Injections of H202 (0.5, 1.0 and 1.5 mu mol/0.2 mu L, n = 6) into the 4th V produced transient (for 10 min) dose-dependent pressor responses. The 1.0 and 1.5 mu mol doses of H2O2 also produced a long lasting bradycardia (at least 24 h with the high dose of H2O2). Prior injection of N-acetyl-L-cysteine (250 nmol/1 mu L/rat) into the 4th V blockade the pressor response and attenuated the bradycardic response to H2O2 (1 mu mol/0.5 mu L/rat, n = 7) into the 4th V. Intravenous (i.v.) atropine methyl bromide (1.0 mg/kg, n = 11) abolished the bradycardia but did not affect the pressor response to H2O2. Prazosin hydrochloride (1.0 mg/kg, n = 6) i.v. abolished the pressor response but did not affect the bradycardia. The increase in the catalase activity (500 UEA/1 mu L/rat injected into the 4th V) also abolished both, pressor and bradycardic responses to H2O2. The results suggest that increased ROS availability into 4th V simultaneously activate sympathetic and parasympathetic outflow inducing pressor and bradycardic responses. (c) 2006 Elsevier Inc. All rights reserved.