DOWNREGULATION OF THE ANGIOTENSIN-CONVERTING ENZYME 2/ANGIOTENSIN-(1-7)/MAS RECEPTOR AXIS IN HEART AND KIDNEY OF TRANSGENIC MICE OVEREXPRESSING GROWTH HORMONE

摘要

Altered function of the renin-angiotensin system (RAS) could be a contributing factor to the cardiac and renal alterations induced by growth hormone (GH) excess. Increased angiotensin (Ang) II levels, arising from the action of Ang converting enzyme (ACE) exerts deletereous effects mediated mainly by the Ang II type 1 (AT1) receptor, whereas the AT2 receptor mediates mostly beneficial effects. The axis of the RAS composed of ACE2, Ang-(1-7) and the Mas receptor counteracts the detrimental effects of Ang II. To further explore this issue, we evaluated the consequences of chronic GH exposure on the in vivo levels of the main components of the RAS in the heart and the kidney of transgenic mice overexpressing bovine GH (bGH mice). At the age of 7–8 months, bGH mice displayed increased sytstolic blood pressure, high degree of both cardiac and renal fibrosis as well as increased levels of markers of tubular and glomerular damage. Angiotensinogen abundance was increased in the liver and the heart of bGH mice, this was concomitant with increased cardiac Ang II immnunostaining. AT1 receptor levels were reduced in the heart and the kidney of bGH mice while AT2 receptor levels were decreased only in the kidney. Importantly, the levels of ACE2, Ang-(1-7) and Mas receptor were markedly decreased in both tissues. The altered profile of expression of the main components of the RAS could contribute to the increased incidence of hypertension, cardiovascular and renal alterations observed in bGH mice.