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THE CARDIAC ANTI‐HYPERTROPHIC EFFECT OF AN ORALLY ACTIVE MAS AGONIST IS ASSOCIATED TO A DECREASE IN BETA‐ARRESTIN IN DOCA‐SALT HYPERTENSIVE RATS.
Author(s) -
Santiago Nívia Maria,
HonoratoSampaio Kinulpe,
Isoldi Mauro C,
Santos Robson AS,
CampagnoleSantos Maria J
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1040.10
Subject(s) - medicine , endocrinology , ventricle , agonist , receptor , muscle hypertrophy , blood pressure , chemistry
In addition to the role of β‐arrestin in AT 1 receptor second messenger desensitization, more recent evidence revealed that β‐arrestins act as scaffolds for numerous signaling networks, such as the MAPKs. On the other hand, Ang‐(1‐7) anti‐trophic effect in the cardiomyocytes can be mediated by alterations in the MAPKs pathways. In this study we evaluated the effect of AVE0991 (AVE), a nonpeptide Ang‐(1‐7) mimic, on the signaling pathways involved in the heart hypertrophy induced by DOCA‐salt hypertension (DSH). After 4 weeks of induction of DSH, rats received AVE (1mg/kg) by gavage for 2 weeks. AVE attenuated the DSH‐induced hypertrophy, as quantified by myocyte diameter measurements (Normotensive rats: 12.97±0.15 μm; DSH: 14.41±0.23 μm; DSH+AVE: 13.39±0.15 μm; n=3 each), without changing the increased blood pressure (tail cuff pletismography). DSH rats showed an increased mRNA expression (real time PCR) of β‐arrestin in the left ventricle (LV) (5.96±1.44 A.U. vs 1.01±0.07 A.U. in normotensive rats; p<0.05) that was blocked after AVE (0.84±0.13 A.U.). In addition, AVE induced an increased AT 1 receptor expression in the LV (1.95±0.32 vs 1.01±0.09 in normotensive rats; p<0.05). No alteration in cardiac adenylate cyclase expression was observed. These data suggest that Ang‐(1‐7) may modulate DSH‐induced cardiac hypertrophy by altering the β‐arrestin pathway. Financial Support: CNPq and INCT