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Role of NO and Superoxide in Hyperhomocysteinemia Induced Cardiac Metabolic Dysfunction in Pregnant Cystathionine Beta‐synthase Heterozygote Mice
Author(s) -
Song Su,
Kertowidjojo Elizabeth,
Ojaimi Caroline,
KandhiI Sharath,
Wolin Michael,
Hintze Thomas H
Publication year - 2012
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.26.1_supplement.1131.15
Subject(s) - cystathionine beta synthase , medicine , endocrinology , hyperhomocysteinemia , homocysteine , apocynin , ascorbic acid , nadph oxidase , chemistry , oxidative stress , biochemistry , amino acid , methionine , food science
Genetic defects in cystathionine beta‐synthase (CBS) can cause severe hyperhomocysteinemia (HHcy). HHcy causes cardiovascular dysfunction and is associated with many complications during pregnancy related to reduced NO bioactivity. This study assessed the mechanisms of HHcy on the NO‐dependent control of cardiac O 2 consumption in pregnant CBS heterozygote (HET) mice. Pregnant CBS HET mice (n=8) were fed low‐folate diet for 20 days to increase plasma Hcy (8.2±0.5 of WT to 17.9±2.2 uM of HET). As compared to wild type (WT) (n=10), while heart weight/body weight increased by 18.2%, ejection fraction decreased from 85.7±0.8% to 80.3±1.8% in HET. Systolic blood pressure was significantly increased from 92.5±3.6 mmHg of WT to 114.5±4.0 mmHg in HET, and MBP from 66.8±9.2 mmHg to 82.9±5.5 mmHg, without hypertension. The total peripheral resistance significantly increased by 42.1%. The ability of bradykinin to reduce myocardial O 2 consumption in vitro was impaired by 56% in heart. The response was restored by ascorbic acid, tempol and apocynin. O 2 − production was increased by 2.7 folds in Hcy heart using lucigenin chemiluminescence. Conclusion CBS deficiency caused HHcy during pregnancy, impairs cardiac function, increases O 2 − production and reduces the ability of NO to regulate myocardial O 2 consumption probably through NADPH oxidase stimulation.