Inhibition of central angiotensin II-induced pressor responses by hydrogen peroxide

Hydrogen peroxide (H₂O₂), important reactive oxygen species produced endogenously, may have different physiological actions. The superoxide anion (O₂^·-) is suggested to be part of the signaling mechanisms activated by angiotensin II (ANG II) and central virus-mediated overexpression of the enzyme superoxide dismutase (that dismutates O₂^·- to H₂O₂) reduces pressor and dipsogenic responses to central ANG II. Whether this result might reflect elevation of H₂O₂ rather than depletion of O₂^·- has not been addressed. Here we investigated the effects of H₂O₂ injected intracerebroventricularly (i.c.v.) or ATZ (3-amino-1,2,4-triazole, a catalase inhibitor) injected intravenously (i.v.) or i.c.v. on the pressor responses induced by i.c.v. injections of ANG II. Normotensive male Holtzman rats (280-320 g, n=5-13/group) with stainless steel cannulas implanted in the lateral ventricle were used. Prior injection of H₂O₂ (5 μmol/1 μl) or ATZ (5 nmol/1 μl) i.c.v. almost abolished the pressor responses induced by ANG II (50 ng/1 μl) also injected i.c.v. (7±3 and 5±3 mm Hg, respectively, vs. control: 19±4 mm Hg). Injection of ATZ (3.6 mmol/kg b.wt.) i.v. also reduced central ANG II-induced pressor responses. Injections of H₂O₂ i.c.v. and ATZ i.c.v. or i.v. alone produced no effect on baseline arterial pressure. Central ANG II, H₂O₂ or ATZ did not affect heart rate. The results show that central injections of H₂O₂ and central or peripheral injections of ATZ reduced the pressor responses induced by i.c.v. ANG II, suggesting that exogenous or endogenous H₂O₂ may inhibit central pressor mechanisms activated by ANG II.