Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus regulates sympathetic nerve activity responses to L-glutamate.

Abstract

Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus regulates sympathetic nerve activity responses to L-glutamate. J Appl Physiol 113: 1423–1431, 2012. First published September 13, 2012; doi:10.1152/japplphysiol.00912.2012.—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 (H2O2) 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 H2O2 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 H2O2 (5 nmol in 100 nl, n 4) and vehicle (artificial cerebrospinal fluid) were without affect, but H2O2, like ATZ, attenuated the increase of RSNA to PVN L-glu (P 0.05). Tonic effects of endogenous H2O2 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 H2O2 tonically, but submaximally, suppresses RSNA responses to L-glu, supporting the idea that a change of H2O2 availability within PVN could influence SNA regulation under physiological and/or disease conditions.