Murine recombinant ACE2 administration (1 mg/kg) obliterated Ang II-induced hypertension in mice and sustained serum ACE2 activity, highlighting species-specific differences in ACE2 inhibition.
Does murine recombinant ACE2 administration increase serum ACE2 activity and reduce Ang II-induced hypertension in mice?
Murine ACE2 administration effectively increases serum ACE2 activity and abolishes Ang II-induced hypertension in mice, revealing important species-specific differences in ACE2 kinetics and inhibitor susceptibility.
A newly produced murine recombinant angiotensin (Ang)-converting enzyme 2 (ACE2) was characterized in vivo and in vitro. The effects of available ACE2 inhibitors (MLN-4760 and 2 conformational variants of DX600, linear and cyclic) were also examined. When murine ACE2 was given to mice for 4 weeks, a marked increase in serum ACE2 activity was sustainable. In acute studies, mouse ACE2 (1 mg/kg) obliterated hypertension induced by Ang II infusion by rapidly decreasing plasma Ang II. These effects were blocked by MLN-4760 but not by either form of DX600. In vitro, conversion from Ang II to Ang-(1-7) by mouse ACE2 was blocked by MLN-4760 (10(-6) m) but not by either form of DX600 (10(-5) m). Quantitative analysis of multiple Ang peptides in plasma ex vivo revealed formation of Ang-(1-9) from Ang I by human but not by mouse ACE2. Both human and mouse ACE2 led to the dissipation of Ang II with formation of Ang (1-7). By contrast, mouse ACE2-driven Ang-(1-7) formation from Ang II was blocked by MLN-4760 but not by either linear or cyclic DX600. In conclusion, sustained elevations in serum ACE2 activity can be accomplished with murine ACE2 administration, thereby providing a strategy for ACE2 amplification in chronic studies using rodent models of hypertension and cardiovascular disease. Human but not mouse ACE2 degrades Ang I to form Ang-(1-9). There are also species differences regarding rodent and human ACE2 inhibition by known inhibitors such that MLN-4760 inhibits both human and mouse ACE2, whereas DX600 only blocks human ACE2 activity.
Ye et al. (Tue,) conducted a other in Ang II-induced hypertension. Murine recombinant ACE2 was evaluated on Blood pressure and serum ACE2 activity. Murine recombinant ACE2 administration (1 mg/kg) obliterated Ang II-induced hypertension in mice and sustained serum ACE2 activity, highlighting species-specific differences in ACE2 inhibition.