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Chronic treatment with a peroxynitrite scavenger attenuates blood pressure and improves renal hemodynamics in angiotensin II (ANG II) induced hypertensive rats
Author(s) -
Matavelli Luis C,
Wells Joel E,
Castillo Alexander,
Majid Dewan SA
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1160.1
Subject(s) - peroxynitrite , angiotensin ii , endocrinology , chemistry , blood pressure , medicine , nitric oxide , renal function , superoxide , biochemistry , enzyme
ANG II induces the production of both nitric oxide (NO) and superoxide (O 2 − ). NO reacts with O 2 − to form peroxynitrite (ONOO − ). To determine the role of ONOO − in the pathogenesis of ANG II induced hypertension, we examined the responses to chronic administration of the ONOO − scavenger hesperitin (Hesp), an inhibitor of ONOO − ‐mediated nitration of tyrosine, in ANG II induced hypertension. Four groups of Sprague‐Dawley rats were treated for 2‐wks: group 1 (G1) was given ANG II (osmotic minipump, 65ng/min; n=9); G2 was given ANG II + Hesp (oral gavage, 50 mg/kg/day; n=12); G3 was given Hesp alone (n=8); and, G4 was the non‐treated control (n=5). Systolic blood pressure (SBP) was measured every 3–4 days using tail‐cuff plethysmography. ANG II treatment in G1 increased SBP (121 ± 2 to 162 ± 4 mmHg) that was partially attenuated with Hesp treatment in G2 (149 ± 3 mmHg; p <0.05). SBP was similar in G3 and G4 (130 ± 1 and 127 ± 1 mmHg). After 2‐wks of chronic treatment, rats were anesthetized and subjected to renal hemodynamics and excretory function using standard clearance techniques. Renal blood flow was decreased in G1, but it was improved in G2 with Hesp treatment (G1, 7.0 ± 0.4; G2, 8.7 ± 0.2*; G3, 8.1 ± 0.5; G4, 9.1 ± 0.7* ml/min/g; * p <0.05 vs G1). Hesp treatment also increased glomerular filtration rate (G1, 1.11 ± 0.04; G2, 1.29 ± 0.03*; G3, 1.22 ± 0.05; G4, 1.24 ± 0.03 ml/min/g) and sodium excretion (G1, 0.6 ± 0.1; G2, 0.8 ± 0.1*; G3, 0.7 ± 0.1; G4, 0.8 ± 0.1 μmol/min/g) compared to G1. These data indicate that ONOO − plays a mechanistic role in the development of ANG II induced hypertension by influencing renal hemodynamics and excretory function. Supported by NHLBI grant RO1‐HL066432.