Type I Induced Diabetes Increases Circulating ACE2 in Male and Female mRen2.Lewis Hypertensive Rats

Abstract

ACE2 is important in the regulation of Ang II and Ang‐(1‐7) – two peptides that exhibit opposing cardiovascular actions. ACE2 also plays a role in diabetes; however, the issue of whether the enzyme is increased or reduced in experimental models is unresolved. Moreover, to our knowledge, the issue of sex differences in ACE2 expression in diabetes has not been addressed particularly in hypertensive models. Therefore, we determined ACE2 activity in adult male and female mRen2.Lewis (mRen) hypertensive rats made diabetic by a single injection of streptozotocin (15 weeks of age). After 4 weeks, tissues, serum and urine were collected and ACE2 activity was determined by directly measuring the conversion of 125I‐Ang II to 125I‐Ang‐(1‐7) by HPLC in the presence or absence of the ACE2 inhibitor MLN4760 with 1 unit [U] activity equivalent to 1 fmol Ang‐(1‐7) formed/min/ml. Serum ACE2 activities were readily detectable in all groups; the control males were 5‐fold higher in comparison to females [26 ± 7 vs. 4.6 ± 1.0 U, n=4] consistent with our previous data in the mRen kidney. However, in the diabetic males, ACE2 activity increased 2.5‐fold [62 ± 10 U, p<0.05] while females exhibited a 10‐fold increase [55 ± 12 U, p<0.05]. We conclude that serum ACE2 activity is significantly increased in the diabetic mRen irrespective of sex and may constitute a compensatory mechanism to enhance the plasma Ang‐(1‐7) – Ang II balance. Funding: HL‐56973, HL‐51952.