TY - JOUR
T1 - Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus regulates sympathetic nerve activity responses to L-glutamate
AU - Cardoso, Leonardo M.
AU - Colombari, Eduardo
AU - Toney, Glenn M.
PY - 2012/11/1
Y1 - 2012/11/1
N2 - The hypothalamic paraventricular nucleus (PVN) is important for maintenance of sympathetic nerve activity (SNA) and cardiovascular function. PVNmediated increases of SNA often involve the excitatory amino acid L-glutamate (L-glu), whose actions can be positively and negatively modulated by a variety of factors, including reactive oxygen species. Here, we determined modulatory effects of the highly diffusible reactive oxygen species hydrogen peroxide (H 2O 2) on responses to PVN L-glu. Renal SNA (RSNA), arterial blood pressure, and heart rate were recorded in anesthetized rats. L-Glu (0.2 nmol in 100 nl) microinjected unilaterally into PVN increased RSNA (P < 0.05), without affecting mean arterial blood pressure or heart rate. Effects of endogenously generated H 2O 2 were determined by comparing responses to PVN L-glu before and after PVN injection of the catalase inhibitor 3-amino-1,2,4-triazole (ATZ; 100 nmol/200 nl, n = 5). ATZ alone was without effect on recorded variables, but attenuated the increase of RSNA elicited by PVN L-glu (P < 0.05). PVN injection of exogenous H 2O 2 (5 nmol in 100 nl, n = 4) and vehicle (artificial cerebrospinal fluid) were without affect, but H 2O 2, like ATZ, attenuated the increase of RSNA to PVN L-glu (P < 0.05). Tonic effects of endogenous H 2O 2 were determined by PVN injection of polyethylene glycol-catalase (1.0 IU in 200 nl, n = 5). Whereas polyethylene glycol-catalase alone was without effect, increases of RSNA to subsequent PVN injection of L-glu were increased (P < 0.05). From these data, we conclude that PVN H 2O 2 tonically, but submaximally, suppresses RSNA responses to L-glu, supporting the idea that a change of H 2O 2 availability within PVN could influence SNA regulation under physiological and/or disease conditions.
AB - The hypothalamic paraventricular nucleus (PVN) is important for maintenance of sympathetic nerve activity (SNA) and cardiovascular function. PVNmediated increases of SNA often involve the excitatory amino acid L-glutamate (L-glu), whose actions can be positively and negatively modulated by a variety of factors, including reactive oxygen species. Here, we determined modulatory effects of the highly diffusible reactive oxygen species hydrogen peroxide (H 2O 2) on responses to PVN L-glu. Renal SNA (RSNA), arterial blood pressure, and heart rate were recorded in anesthetized rats. L-Glu (0.2 nmol in 100 nl) microinjected unilaterally into PVN increased RSNA (P < 0.05), without affecting mean arterial blood pressure or heart rate. Effects of endogenously generated H 2O 2 were determined by comparing responses to PVN L-glu before and after PVN injection of the catalase inhibitor 3-amino-1,2,4-triazole (ATZ; 100 nmol/200 nl, n = 5). ATZ alone was without effect on recorded variables, but attenuated the increase of RSNA elicited by PVN L-glu (P < 0.05). PVN injection of exogenous H 2O 2 (5 nmol in 100 nl, n = 4) and vehicle (artificial cerebrospinal fluid) were without affect, but H 2O 2, like ATZ, attenuated the increase of RSNA to PVN L-glu (P < 0.05). Tonic effects of endogenous H 2O 2 were determined by PVN injection of polyethylene glycol-catalase (1.0 IU in 200 nl, n = 5). Whereas polyethylene glycol-catalase alone was without effect, increases of RSNA to subsequent PVN injection of L-glu were increased (P < 0.05). From these data, we conclude that PVN H 2O 2 tonically, but submaximally, suppresses RSNA responses to L-glu, supporting the idea that a change of H 2O 2 availability within PVN could influence SNA regulation under physiological and/or disease conditions.
KW - Arterial blood pressure
KW - Catalase
KW - Glutamatergic transmission
KW - Reactive oxygen species
KW - Superoxide dismutase
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U2 - 10.1152/japplphysiol.00912.2012
DO - 10.1152/japplphysiol.00912.2012
M3 - Article
C2 - 22984242
AN - SCOPUS:84868331239
SN - 8750-7587
VL - 113
SP - 1323
EP - 1331
JO - Journal of applied physiology
JF - Journal of applied physiology
IS - 9
ER -