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Angiotensin‐(1–7) administration benefits cardiac, renal and progenitor cell function in db/db mice
Author(s) -
Papinska A M,
Mordwinkin N M,
Meeks C J,
Jadhav S S,
Rodgers K E
Publication year - 2015
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13225
Subject(s) - endocrinology , medicine , progenitor cell , angiotensin ii , bone marrow , bradykinin , inflammation , oxidative stress , fibrosis , kidney , stem cell , receptor , biology , genetics
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, A ng‐(1–7) alone, or A ng‐(1–7) combined with an inhibitor (losartan, PD 123319, A‐779, L ‐ NAME or icatibant) daily for 14 days. Key Results An improvement in physiological heart function was observed in A ng‐(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 MAS 1, AT 2 and bradykinin receptors and inhibition of NO formation. Treatment with A ng‐(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 A ng‐(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.