title: Oxidant stress and blood pressure responses to angiotensin II administration in rats fed varying salt diets.
abstract: To examine the hypothesis that NAD(P)H oxidase (Nox)-derived superoxide generation is involved in the development of angiotensin II (ANG II)-induced hypertension, we evaluated the responses to ANG II infusion (65 ng/min; osmotic mini-pump) for 2 weeks in rats treated with or without apocynin (APO) (inhibitor of Nox subunits assembly) in drinking water (12 mmol/L). Rats were grouped according to their diets with varying salt content (normal salt [NS], 0.4%; high salt [HS], 8%; low salt [LS], 0.03%) given during the 2-week experimental period. The variation in salt intake did not alter mean arterial pressure (MAP, recorded via pre-implanted arterial catheter) but showed proportionate levels in urinary excretion rate of Isoprostaglandin(2alpha) (U(ISO)V; NS, 179 +/- 26; HS, 294 +/- 38; LS, 125 +/- 7 ng/kg/24 h). Treatment with ANG II increased MAP proportional to salt intake (NS, 126 +/- 3 to 160 +/- 5; HS, 116 +/- 4 to 184 +/- 5; LS, 125 +/- 1 to 154 +/- 5 mm Hg). However, ANG II increased U(ISO)V only in NS rats (250 +/- 19 ng/kg/24 h) but not in HS or LS rats. In response to ANG II, Nox subunits protein expression increased in HS but not in the NS or LS rats. Apocynin treatment partially ameliorated these changes in Nox proteins in HS rats but did not alter ANG II-induced increases in MAP or U(ISO)V. These data suggest that Nox activation may not be the sole factor or alternatively, that a constitutively active isoform of Nox is involved in oxidative stress mechanism that is associated with dietary salt or ANG II-induced hypertension.
authors.affiliation: Department of Physiology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Pech
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Sikka
authors.forename: Ram K
authors.initials: RK
authors.lastname: Sindhu
authors.forename: Nostarola D
authors.initials: ND
authors.lastname: Vaziri
authors.forename: Dewan S A
authors.initials: DS
authors.lastname: Majid
mesh_terms: D000098:Acetophenones / Q000627:therapeutic use; D000804:Angiotensin II / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D015153:Blotting, Western; D004039:Diet, Sodium-Restricted; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006973:Hypertension / Q000139:chemically induced / Q000628:therapy / Q000652:urine; D007262:Infusions, Intravenous; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000633:toxicity
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C075750:8-epi-prostaglandin F2alpha; C056165:acetovanillone; D015237:Dinoprost