P181 AGE-RELATED CHANGES IN THE PROTECTIVE AXIS OF THE RENIN-ANGIOTENSIN SYSTEM IN THE BRAIN OF NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

Background and Objective. Aging is a major risk factor for the development of hypertension, that leads to end organ damage and cognitive dysfunction. The axis of the renin-angiotensin system composed of angiotensin (Ang) (1-7) the Mas receptor (MasR) and angiotensin converting enzyme 2 (ACE2) plays a cerebroprotective role by increasing blood flow, angiogenesis and improving cognitive function among others. Evidence on the expression of this axis with age is limited. We investigated Ang-(1-7)/Mas/ACE2 axis in different areas of the brain from normotensive and spontaneously hypertensive rats (SHR). Methods. Hypothalamus (HT), brainstem (BS), hippocampus (HC) and cerebral cortex (CC) were isolated from Wistar normotensive rats and SHR of 1, 3 and 12 months. Ang-(1-7) levels were measured by radioimmunoassay and ACE2 and MasR abundance was determined by immunoblotting. Results. Ang-(1-7) levels decreased with age in all the areas from normotensive rats and in CC from SHR, while it increased from 1 to 3 months but then decreased at 12 months in BS, HC and HT from SHR. There was no difference in Ang-(1-7) levels between normotensive and SHR except at 1 month of age where Ang-(1-7) levels were lower in BS, HC and HT but the same in CC from SHR compared to normotensive rats. MasR and ACE2 expression did not change with age in all the investigated areas from normotensive rats and in CC from SHR. However, MasR and ACE2 increased with age in HC from SHR and they were higher than in normotensive rats. Conclusions. Our results showed changes in the expression of the brain Ang-(1-7)/Mas/ACE2 axis which may contribute to deleterious functions observed in the brain with age.