Increase in ACE2 and Neprilysin Activity in the Hypothalamus of (mRen2)27 Transgenic Rats

Abstract

Angiotensin converting enzyme (ACE), ACE2 and neprilysin, key enzymes in the renin-angiotensin system (RAS), are involved in the formation of angiotensin (Ang ) II and Ang-(1–7). Both peptides plays are major players in the modulation of fluid balance and cardiovascular function. The regulation of the enzymes responsible for their formation and metabolism in the hypothalamus over the long term is not known. We measured ACE, ACE2 and neprilysin mRNA in hypothalamic tissue of Sprague-Dawley (SD) and (mRen2)27 transgenic rats with over-expression of brain renin using using real time PCR. ACE mRNA was not different between the two strains (1.036 ± 0.07 vs 1.132 ± 0.14 relative gene expression). ACE2 and neprilysin mRNAs were ~30% and 60% higher, respectively, in tissue obtained from (mRen2)27 rats compared with SD rats. The lack of downregulation of ACE may account for the 10-fold elevation of Ang II in the hypothalamus of (mRen2)rats. We speculate that the increases in neprilysin and ACE2 would account for greater metabolism of Ang II and the increase in formation of Ang-(1–7) in the (mRen2)rats as a compensatory mechanism. (Support: HL-51952)