Lifetime overproduction of circulating Angiotensin-(1-7) attenuates deoxycorticosterone acetate-salt hypertension-induced cardiac dysfunction and remodeling.
We evaluated the development of arterial hypertension, cardiac function, and collagen deposition, as well as the level of components of the renin-angiotensin system in the heart of transgenic rats that overexpress an angiotensin (Ang)-(1-7)-producing fusion protein, TGR(A1-7)3292 (TG), which induces a lifetime increase in circulating levels of this peptide. After 30 days of the induction of the deoxycorticosterone acetate (DOCA)-salt hypertension model, DOCA-TG rats were hypertensive but presented a lower systolic arterial pressure in comparison with DOCA-Sprague-Dawley (SD) rats. In contrast to DOCA-SD rats that presented left ventricle (LV) hypertrophy and diastolic dysfunction, DOCA-TG rats did not develop cardiac hypertrophy or changes in ventricular function. In addition, DOCA-TG rats showed attenuation in mRNA expression for collagen type I and III compared with the increased levels of DOCA-SD rats. Ang II plasma and LV levels were reduced in SD and TG hypertensive rats in comparison with normotensive animals. DOCA-TG rats presented a reduction in plasma Ang-(1-7) levels; however, there was a great increase in Ang-(1-7) ( approximately 3-fold) accompanied by a decrease in mRNA expression of both angiotensin-converting enzyme and angiotensin-converting enzyme 2 in the LV. The mRNA expression of Mas and Ang II type 1 receptors in the LV was not significantly changed in DOCA-SD or DOCA-TG rats. This study showed that TG rats with increased circulating levels of Ang-(1-7) are protected against cardiac dysfunction and fibrosis and also present an attenuated increase in blood pressure after DOCA-salt hypertension. In addition, DOCA-TG rats showed an important local increase in Ang-(1-7) levels in the LV, which might have contributed to the attenuation of cardiac dysfunction and prefibrotic lesions.
Santiago
Nívia M
NM
Laboratory of Hypertension and Instituto Nacional de Ciência e Tecnologia-Nanobiofar, Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-ICB, UFMG, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
Guimarães
Priscila S
PS
Sirvente
Raquel A
RA
Oliveira
Laser A M
LA
Irigoyen
Maria C
MC
Santos
Robson A S
RA
Campagnole-Santos
Maria J
MJ
D000704:Analysis of Variance; D000803:Angiotensin I / Q000097:blood / Q000235:genetics*; D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D003900:Desoxycorticosterone / Q000494:pharmacology*; D006334:Heart Function Tests; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D010446:Peptide Fragments / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D012084:Renin-Angiotensin System / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020257:Ventricular Remodeling / Q000235:genetics*
D024042:Collagen Type I; D024061:Collagen Type III; D010446:Peptide Fragments; D012333:RNA, Messenger; D003900:Desoxycorticosterone; D000803:Angiotensin I; C118790:angiotensin I (1-7)