Angiotensin-(1-7) improves cardiac remodeling and inhibits growth-promoting pathways in the heart of fructose-fed rats.

J. F. GIANI; M. C. MUÑOZ; M. A. MAYER; L. C. VEIRAS; C. ARRANZ; C. TAIRA; D. TURYN; J. TOBLLI; F. P. DOMINICI

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Año: 2010 vol. 298 p. 1003 - 1012

0363-6135

The presentstudy examined whether chronic treatment with angiotensin (ANG)-(1–7) reduces cardiac remodeling and inhibits growth-promotingsignaling pathways in the heart of fructose-fed rats (FFR), an animalmodel of insulin resistance. Sprague-Dawley rats were fed eithernormal rat chow (control) or the same diet plus 10% fructose indrinking water. For the last 2 wk of a 6-wk period of the correspond-ing diet, control and FFR were implanted with osmotic pumps thatdelivered ANG-(1–7) (100 ng·kg
1·min
1). A subgroup of eachgroup of animals (control or FFR) underwent a sham surgery. Wedetermined heart weight, myocyte diameter, interstitial fibrosis, andperivascular collagen type III deposition as well as the phosphoryla-tion degree of ERK1/2, JNK1/2, and p38MAPK. FFR showed a mildhypertension that was significantly reduced after ANG-(1–7) treat-ment. Also, FFR displayed higher ANG II circulating and local levelsin the heart that remained unaltered after chronic ANG-(1–7) infusion.An increased heart-to-body weight ratio, myocyte diameter, as well asleft ventricular fibrosis and perivascular collagen type III depositionwere detected in the heart of FFR. Interestingly, significant improve-ments in these cardiac alterations were obtained after ANG-(1–7)treatment. Finally, FFR that received ANG-(1–7) chronically dis-played significantly lower phosphorylation levels of ERK1/2, JNK1/2,and p38MAPK. The beneficial effects obtained by ANG-(1–7) wereassociated with normal values of Src-homology 2-containing protein-tyrosine phosphatase-1 (SHP-1) activity in the heart. In conclusion,chronic ANG-(1–7) treatment ameliorated cardiac hypertrophy andfibrosis and attenuated the growth-promoting pathways in the heart.These findings show an important protective role of ANG-(1–7) in theheart of insulin-resistant rats.