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High salt intake attenuates antihypertensive action of angiotensin II receptor blockade with induction of renal oxidative stress
Author(s) -
Endo Satoshi,
Mori Takefumi,
Yoneki Yoshimi,
Tokudome Goro,
Hosoya Tatsuo,
Ito Sadayoshi
Publication year - 2006
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.20.4.a755-a
Subject(s) - oxidative stress , angiotensin ii , endocrinology , olmesartan , medicine , chemistry , excretion , reactive oxygen species , angiotensin receptor , mean arterial pressure , receptor , blood pressure , heart rate , biochemistry
We tested the hypothesis that oxidative stress is involved in high salt diet(HS)‐induced attenuation of antihypertensive action of angiotensin II receptor blocker(ARB). Sprague‐Dawley rats were assigned to four groups; 1) vehicle group, 2) ARB olmesartan (OLM, 0.1umol/kg/hr) group, 3) slow pressor dose of angiotensin II (AII, 100ng/kg/min) group, 4) AII+OLM group. Drugs were infused subcutaneously with osmotic pump for 14 days. Rats were fed a normal salt diet (NS, 0.5%NaCl) and then a HS diet (8%NaCl) for 7 days each. Mean arterial pressure (MAP) was measured continuously with radio‐telemetry system. 24 hour urinary H 2 O 2 excretion and serum diacron reactive oxygen metabolites (D‐ROM) were measured. MAP did not differ with either diet in vehicle group (n=4). OLM reduced MAP by 18.6+/−2.4 mmHg (n=5) during NS, which was abolished with HS. AII had no effect during NS, but increased MAP by 19.6 +/− 6.1 mmHg (n=6) during HS. AII+OLM reduced MAP by 20.9+/− 2.6 mmHg (n=4) during NS, which was abolished with HS. In all groups, urinary H 2 O 2 excretion increased significantly during HS but NS. D‐ROM did not change with HS in any group. These results show that HS attenuates antihypertensive action of ARB and increases urinary but not serum oxidative stress marker. We conclude that HS‐induced increases in renal oxidative stress may attenuate ARB’s action.