In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 60, No. suppl_1 ( 2012-09)
Abstract:
Diabetic nephropathy (DN) is a major microvascular complication of diabetes involving oxidative stress and endothelial damage. Nitrosonifedipine (NO-NIF) is converted from nifedipine under the light illumination. The ability of NO-NIF to block calcium channels is quite weak compared with that of nifedipine. Recently, we have demonstrated that NO-NIF reacts with unsaturated fatty acid leading to generate NO-NIF radical, which acquires radical scavenging activity. Also we have reported that NO-NIF reduces cytotoxicity of tumor necrosis factor-α (TNF-α) in cultured human glomerular endothelial cells. However, it is unclear the effects of NO-NIF on the pathogenesis related with oxidative stress, such as DN. In this study, we investigated whether NO-NIF treatment improves DN by using KKAy mice developing type II diabetes. Urinary albumin (UA) and total urinary protein (TUP) were elevated in KKAy mice (16 weeks old) compared with C57BL/6 mice, which were significantly decreased by NO-NIF treatment (30 mg/kg/day, i.p., 4 weeks) (UA; 1415.2 ± 312.5 vs 609.6 ± 151.5 μg/24hr, p 〈 0.05, TUP; 73.1 ± 11.2 vs 44.8 ± 9.4 mg/24hr, p 〈 0.05). Mesangial expansion was estimated by PAS staining. Glomerular diameter (GD) and glomerular tuft area (GTA) were extended in KKAy mice compared with C57BL/6 mice, which were significantly decreased by NO-NIF treatment (GD; 81.4 ± 2.6 vs 65.7 ± 1.9 μm, p 〈 0.05, GTA; 4198.8 ± 254.6 vs 3051.9 ± 140.4 μm2, p 〈 0.05). NO-NIF significantly suppressed urinary 8-hydroxy-20-deoxyguanosine (144.1 ± 21.4 vs 75.2 ± 11.1 ng/24hr, p 〈 0.05) in KKAy mice. Also NO-NIF reduced the elevation of reactive oxygen species in kidney of KKAy mice detected by DHE staining. However NO-NIF had no influence on SOD activity in kidney. NO-NIF significantly inhibited the mRNA expression of TNF-α in kidney of KKAy mice (2.9 ± 0.1 vs 1.9 ± 0.1 fold increase, p 〈 0.05). ICAM-1 protein expression was increased in glomeruli of KKAy mice, which was decreased by NO-NIF treatment. On the other hand, NO-NIF had no effect on glucose tolerance and systolic blood pressure (111.1 ± 2.3 vs 108.3 ± 3.3 mmHg, N.S.) in KKAy mice. These findings suggest that NO-NIF prevents the progression of DN via the attenuation of oxidative stress independent of antihypertensive or antihyperglycemic action.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/hyp.60.suppl_1.A371
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2012
detail.hit.zdb_id:
2094210-2
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