Key Points
- To determine the extent to which cardiac ACE2 mediates the conversion of angiotensin II into angiotensin-(1-7) in hypertensive compared to normotensive rat hearts.
- Isolated hearts from male normotensive Sprague-Dawley [Tg(-)] and hypertensive [mRen2]27 [Tg(+)] rats were evaluated using a Langendorff preparation with a 60-minute recirculation of 10 nM angiotensin II.
- Cardiac effluent was assayed for angiotensin-(1-7) generation and ACE2 activity in the presence and absence of the selective ACE2 inhibitor MLN-4760 (1 μM).
- Total angiotensin-(1-7) formation from angiotensin II peaked at 30 minutes and was equivalent between normotensive (510 ± 55 pM, n=20) and hypertensive hearts (497 ± 63 pM, n=14).
- ACE2 inhibition with MLN-4760 decreased angiotensin-(1-7) production by 83% in hypertensive Tg(+) hearts (57 ± 19 pM, P<0.01, n=7), but showed no significant effect in normotensive Tg(-) hearts (285 ± 53 pM, P>0.05, n=10).
- Effluent ACE2 enzymatic activity correlated strongly with cardiac ACE2 protein expression levels across perfused hearts (r=0.78).
Structured PICO
PPopulationIsolated hearts from male normotensive Sprague-Dawley [Tg(-)] and hypertensive [mRen2]27 [Tg(+)] rats
IInterventionACE2 inhibition (MLN-4760, 1 microM) during a 60-min recirculation period with 10 nM ANG II
CComparatorNo ACE2 inhibition (or comparison between Tg(+) and Tg(-) rats)
OOutcomeANG-(1-7) generation from ANG II in the cardiac effluentsurrogate
ACE2 plays a direct role in the metabolism of cardiac ANG II to ANG-(1-7) in the hypertrophic hearts of hypertensive rats, which may be a compensatory response to cardiac remodeling.