Inhibition of central angiotensin II-induced pressor responses by hydrogen peroxide.
Hydrogen peroxide (H(2)O(2)), important reactive oxygen species produced endogenously, may have different physiological actions. The superoxide anion (O(2)(·-)) 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 O(2)(·-) to H(2)O(2)) reduces pressor and dipsogenic responses to central ANG II. Whether this result might reflect elevation of H(2)O(2) rather than depletion of O(2)(·-) has not been addressed. Here we investigated the effects of H(2)O(2) 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 H(2)O(2) (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 H(2)O(2) i.c.v. and ATZ i.c.v. or i.v. alone produced no effect on baseline arterial pressure. Central ANG II, H(2)O(2) or ATZ did not affect heart rate. The results show that central injections of H(2)O(2) and central or peripheral injections of ATZ reduced the pressor responses induced by i.c.v. ANG II, suggesting that exogenous or endogenous H(2)O(2) may inhibit central pressor mechanisms activated by ANG II.
Lauar
M R
MR
Department of Physiology and Pathology, Dentistry School, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil.
Colombari
D S A
DS
De Paula
P M
PM
Colombari
E
E
Cardoso
L M
LM
De Luca
L A
LA
Menani
J V
JV
D000640:Amitrole / Q000008:administration & dosage / Q000494:pharmacology; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002374:Catalase / Q000037:antagonists & inhibitors; D006339:Heart Rate / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000804:Angiotensin II; D006861:Hydrogen Peroxide; D002374:Catalase; D000640:Amitrole