Male Mice Exhibit Less ACE2 Activity in the Lung Relative to Females

Throughout much of their lives, men have higher blood pressure and a greater incidence of hypertension than women. However, the underlying causes of this difference remain to be elucidated. A key factor that has recently been found to regulate blood pressure is Angiotensin Converting Enzyme II (ACE2). The activity of this enzyme in relation to hypertension has been of great interest, and has to date been investigated primarily in the kidney. Involved in the renin‐angiotensin system (RAS), ACE2 converts the vasoconstrictor Ang II to the vasodilator Ang‐(1‐7). In this study, we will investigate Ang II induced hypertension by measuring ACE2 activity in lung within the Sry transgenic mouse model. By using the Sry four core genotype model, we plan to separate differences in gonadal hormone milieu from other differences caused by sex chromosome complements. Previous enzyme assays of lung ACE2 activity had been hampered by background noise and low levels of activity. However, we have developed an assay with increased substrate sensitivity with an optimized signal to noise ratio. We hypothesize that both males and females will exhibit higher rates of lung ACE2 activity after Ang II infusion, and that females will exhibit a higher rate of lung ACE2 activity in both control and Ang II treatments. Furthermore, this increased activity of ACE2 should be due to differences in gonadal hormone milieu rather than sex chromosome complement.