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Regulation of cardiac NO bioactivity in response to low salt diet: A time course study on the role of NADPH oxidase.
Author(s) -
Skayian Yester,
He Arthur Yu,
Ojaimi Caroline,
Hintze Thomas H
Publication year - 2009
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.23.1_supplement.628.15
Subject(s) - nadph oxidase , apocynin , losartan , chemistry , endocrinology , medicine , oxidase test , bradykinin , angiotensin ii , stimulation , receptor , pharmacology , oxidative stress , enzyme , biochemistry
A time dependent study of low salt diet (LSD) was conducted on wild type (WT) male mice to assess its effects on ANG II, cardiac MVO2 and NO bioactivity. WT mice on a LSD for 2 weeks showed an increase in plasma ANG II levels (207 ± 46 to 502 ± 65 pg/ml (n=6), P<0.005) with no significant increase in blood pressure. Microarray analysis revealed a large number of significantly expressed genes in LSD mice, 153 genes up‐regulated and 399 genes down‐regulated (P<0.05). Genes related to NOS, ANG II, AT1 receptor, and NADPH oxidase did not show any significant change between LSD and normal diet (ND) fed mice. Accordingly, mice were put on LSD for 8 weeks. On ND, stimulation of NO production by bradykinin (BK) induced a concentration dependent reduction in MVO2 (‐18 ± 1%) in vitro. BK‐induced reduction in MVO2 was significantly attenuated in WT mice (‐12 ± 1%, P<0.0001) on LSD. The attenuated BK‐induced reduction in MVO2 was restored by tiron (‐22 ± 2%), apocynin (‐25 ± 3%), or by losartan (‐18 ± 2%), on LSD. Similar effects were seen in WT mice on LSD for 2 weeks. Blood pressure was also significantly increased after 8 weeks on LSD (127±1/73±2 to 146±4/90±5 (n=11), P<0.0001). These findings suggest that increased plasma ANG II levels with LSD reduce NO bioavailability and alter the control of cardiac O2 consumption by NO. The assembly and activation of NADPH oxidase by ANG II may be the basis of low salt induced cardiac dysfunction. Supported by HL 50142.