title: Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus regulates sympathetic nerve activity responses to L-glutamate.
abstract: The hypothalamic paraventricular nucleus (PVN) is important for maintenance of sympathetic nerve activity (SNA) and cardiovascular function. PVN-mediated 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(2)O(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(2)O(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(2)O(2) (5 nmol in 100 nl, n = 4) and vehicle (artificial cerebrospinal fluid) were without affect, but H(2)O(2), like ATZ, attenuated the increase of RSNA to PVN L-glu (P < 0.05). Tonic effects of endogenous H(2)O(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(2)O(2) tonically, but submaximally, suppresses RSNA responses to L-glu, supporting the idea that a change of H(2)O(2) availability within PVN could influence SNA regulation under physiological and/or disease conditions.
authors.affiliation: Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
authors.forename: Leonardo M
authors.initials: LM
authors.lastname: Cardoso
authors.forename: Eduardo
authors.initials: E
authors.lastname: Colombari
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Toney
mesh_terms: D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D007668:Kidney / Q000294:innervation / Q000502:physiology; D008297:Male; D008845:Microinjections; D010286:Paraventricular Hypothalamic Nucleus / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D000640:Amitrole