Angiotensin-(1-7) administration benefits cardiac, renal and progenitor cell function in db/db mice

被引:41
作者
Papinska, A. M. [1 ]
Mordwinkin, N. M. [1 ]
Meeks, C. J. [1 ]
Jadhav, S. S. [1 ]
Rodgers, K. E. [1 ]
机构
[1] Univ So Calif, Sch Pharm, Los Angeles, CA 90033 USA
基金
美国国家卫生研究院;
关键词
NITRIC-OXIDE SYNTHASE; OXIDATIVE STRESS; ENDOTHELIAL DYSFUNCTION; DIABETIC-NEPHROPATHY; CONCISE GUIDE; HEART; PHARMACOLOGY; EXPRESSION; MOBILIZATION; INFLAMMATION;
D O I
10.1111/bph.13225
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
BACKGROUND AND PURPOSE Diabetic patients are at an increased risk of cardiovascular disease, in part due to inflammation and oxidative stress. These two pathological mechanisms also affect other organs and cells including the kidneys and progenitor cells. Angiotensin-(1-7) [Ang-(1-7)] has previously been shown to counterbalance pathological effects of angiotensin II, including inflammation and oxidative stress. The aim of this study was to investigate the effects of short-term (2 weeks) Ang-(1-7) treatment on cardiovascular and renal function in a mouse model of type 2 diabetes (db/db). EXPERIMENTAL APPROACH Eight- to nine-week-old db/db mice were administered either vehicle, Ang-(1-7) alone, or Ang-(1-7) combined with an inhibitor (losartan, PD123319, A-779, L-NAME or icatibant) daily for 14 days. KEY RESULTS An improvement in physiological heart function was observed in Ang-(1-7)-treated mice. Ang-(1-7) also reduced cardiomyocyte hypertrophy, fibrosis and inflammatory cell infiltration of the heart tissue and increased blood vessel number. These changes were blocked by antagonists of the MAS1, AT(2) and bradykinin receptors and inhibition of NO formation. Treatment with Ang-(1-7) reduced glomerular damage and oxidative stress in kidney tissue. Bone marrow and circulating endothelial progenitors, as well as bone marrow mesenchymal stem cells, were increased in mice treated with Ang-(1-7). CONCLUSIONS AND IMPLICATIONS Short-term Ang-(1-7) treatment of young db/db mice improved heart function and reduced kidney damage. Treatment also improved bone marrow and circulating levels of endothelial and mesenchymal stem cells. All of this may contribute to improved cardiovascular and renal function.
引用
收藏
页码:4443 / 4453
页数:11
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