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Poster Sesion I with Reception

Abstract 121: Cytochrome P450 1B1 Gene Disruption Prevents Cardiac Dysfunction Associated With DOCA-salt-induced Hypertension in Mice

Brett L Jennings, Anne M Estes, Fariborz A Yaghini, Zheng Fan, Kafait U Malik
Hypertension. 2012;60:A121
Brett L Jennings
Univ of Tennessee, Memphis, TN
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Anne M Estes
Univ of Tennessee, Memphis, TN
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Fariborz A Yaghini
Univ of Tennessee, Memphis, TN
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Zheng Fan
Univ of Tennessee, Memphis, TN
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Kafait U Malik
Univ of Tennessee, Memphis, TN
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Abstract

Previously, we have shown that cytochrome P450 (CYP) 1B1 contributes to deoxycorticosterone acetate (DOCA) salt-induced hypertension and associated increase in vascular reactivity, endothelial dysfunction, and vascular oxidative stress in rats. This study was conducted to determine whether Cyp1b1 gene disruption protects against cardiac dysfunction, measured by echocardiography, in this model of hypertension in mice. Eight week old male mice were uninephrectomized, subcutaneously implanted with a DOCA pellet (50mg/kg) and given 1% saline in drinking water for 4 weeks, and blood pressure (BP) was measured weekly by tail cuff method. DOCA-salt treatment increased systolic BP in Cyp1b1+/+ mice to a greater degree than in Cyp1b1-/- mice (115 ± 3 to 188 ± 5 mmHg vs. 120 ± 5 to 152 ± 8 mmHg, respectively, P < 0.05). DOCA-salt treatment produced cardiac dysfunction, as indicated by decreased fractional shortening (FS), ejection fraction (EF), and the ratio of peak early to late diastolic mitral annulus velocities (E′/A′), and an increase in both end-diastolic volume and end-systolic volume, in Cyp1b1+/+, but not Cyp1b1-/- mice (Table 1). Cardiac production of reactive oxygen species, as indicated by 2-hydroxyethidium fluorescence intensity, was increased in DOCA-salt treated Cyp1b1+/+ mice, which was attenuated in Cyp1b1-/- mice. These data suggest that Cyp1b1 plays a pivotal role in cardiac dysfunction associated with DOCA-salt hypertension in mice by increasing oxidative stress, and that it could serve as a potential target for drugs to treat cardiovascular dysfunction associated with excess mineralocorticoid-salt hypertension.

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    Abstract 121: Cytochrome P450 1B1 Gene Disruption Prevents Cardiac Dysfunction Associated With DOCA-salt-induced Hypertension in Mice
    Brett L Jennings, Anne M Estes, Fariborz A Yaghini, Zheng Fan and Kafait U Malik
    Hypertension. 2012;60:A121, originally published October 14, 2015

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    Abstract 121: Cytochrome P450 1B1 Gene Disruption Prevents Cardiac Dysfunction Associated With DOCA-salt-induced Hypertension in Mice
    Brett L Jennings, Anne M Estes, Fariborz A Yaghini, Zheng Fan and Kafait U Malik
    Hypertension. 2012;60:A121, originally published October 14, 2015
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