In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 64, No. suppl_1 ( 2014-09)
Abstract:
A role for Nox4 in hypertension remains in question. Both protective and injurious Nox4-dependent renal and cardiovascular effects have been reported. We assessed whether gene-targeted Nox4 deficiency (Nox4 -/- mice) could affect development of hypertension, cardiac hypertrophy and renal function in a model of chronic angiotensin II (AngII)-dependent hypertension. We studied mice transgenic for active human renin under the control of the transthyretin promoter (LinA3 mice); these mice develop hypertension over the course of their lifespan. Four genotypes of mice were generated: Wild-type (WT), LinA3, Nox4 -/- , and LinA3/Nox4 -/- . Nox4-deficiency prevented the development of hypertension (LinA3: 154 vs LinA3/Nox4 -/- : 135 mmHg) and cardiac hypertrophy (LinA3: 2.55 vs LinA3/Nox4 -/- : 1.73 mg/g) observed in LinA3 mice ( P 〈 0.05) and was associated with reduced systemic oxidative stress (Plasma TBARS - LinA3: 2.13 vs LinA3/Nox4 -/- : 1.71 mM) . Furthermore, cardiac collagen content was decreased in Nox4 -/- versus LinA3 mice. While Nox4 deficiency attenuated hypertension in LinA3 mice, it yielded detrimental effects on renal function. Specifically, albumin-to-creatinine ratio was significantly elevated in LinA3/Nox4 -/- mice compared with LinA3, Nox4 -/- and WT littermates. LinA3 mice showed evidence of mild segmental glomerulosclerosis. LinA3/Nox4 -/- mice developed severe renal lesions including increased glomerular tuft to fibrotic area, global glomerulosclerosis with numerous foci containing perivascular and peritubular monocyte/macrophage cell infiltration. These findings demonstrate that while global Nox4 deletion may be protective for cardiac pathology and hypertension it is conducive to renal injury in a model of chronic AngII-mediated hypertension. Our data indicate tissue-specific effects of Nox4, which may explain divergent renal and cardiac Nox4 actions in Ang II-dependent hypertension.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/hyp.64.suppl_1.630
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2014
detail.hit.zdb_id:
2094210-2
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