ET A Receptor Blockade Decreases Vascular Superoxide Generation in DOCA-Salt Hypertension

• DOI: 10.1161/01.hyp.0000088363.65943.6c
• Publication Date: 2003-08-12T02:38:18Z
• Authors: Glaucia E. Callera; Rhian M. Touyz; Simone A. Teixeira; Marcelo N. Muscara; Maria Helena C. C...; Zuleica B. Fortes; Dorothy Nigro; Ernesto L. Schiffrin; Rita C. Tostes
• Keywords: Nitrotyrosine

Development and progression of end-organ damage in hypertension have been associated with increased oxidative stress. Superoxide anion accumulation has reported deoxycorticosterone acetate (DOCA)-salt hypertension, which endothelin-1 plays an important role cardiovascular damage. We hypothesized that blockade ET A receptors DOCA-salt rats would decrease Both systolic blood pressure (SBP, 210±9 mm Hg; P <0.05) vascular superoxide generation vivo were (44.9±10.3% ethidium bromide–positive nuclei; versus control uninephrectomized (UniNx) (118±3 18.5±3%, respectively). In rats, the antagonist BMS 182874 (40 mg/kg per day PO) lowered SBP (170±4 UniNx, 120±3 Hg) normalized production (21.7±6 11.9±7%). Vitamin E (200 decreased formation (18.8±7%) but did not alter SBP. Oxidative stress nonstimulated circulating polymorphonuclear cells (PMNs) or PMNs treated zymosan, inducer release, was similar UniNx groups. by unaffected treatment 182874. Western blot analysis showed nitrotyrosine-containing proteins mesenteric vessels from compared UniNX. Treatment either vitamin abolished differences between Maximal relaxation to acetylcholine aortas (75.8±4.2% 95.4±1.9%, <0.05). acetylcholine-induced 93.5±4.5%. These findings indicate is activation endothelin system through apparently pressure–independent fashion.