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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Br+J+Pharmacol
2015 ; 172
(18
): 4443-4453
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Angiotensin-(1-7) administration benefits cardiac, renal and progenitor cell
function in db/db mice
#MMPMID26075703
Papinska AM
; Mordwinkin NM
; Meeks CJ
; Jadhav SS
; Rodgers KE
Br J Pharmacol
2015[Sep]; 172
(18
): 4443-4453
PMID26075703
show ga
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.