Activation of the Neuroprotective Angiotensin-Converting Enzyme 2 in Rat Ischemic Stroke [Renin-Angiotensin System]

The angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis represents a promising target for inducing stroke neuroprotection. Here, we explored stroke-induced changes in expression and activity of endogenous angiotensin-converting enzyme 2 and other system components in Sprague–Dawley rats. To evaluate the clinical feasibility of treatments that target this axis and that may act in synergy with stroke-induced changes, we also tested the neuroprotective effects of diminazene aceturate, an angiotensin-converting enzyme 2 activator, administered systemically post stroke. Among rats that underwent experimental endothelin-1–induced ischemic stroke, angiotensin-converting enzyme 2 activity in the cerebral cortex and striatum increased in the 24 hours after stroke. Serum angiotensin-converting enzyme 2 activity was decreased within 4 hours post stroke, but rebounded to reach higher than baseline levels 3 days post stroke. Treatment after stroke with systemically applied diminazene resulted in decreased infarct volume and improved neurological function without apparent increases in cerebral blood flow. Central infusion of A-779, a Mas receptor antagonist, resulted in larger infarct volumes in diminazene-treated rats, and central infusion of the angiotensin-converting enzyme 2 inhibitor MLN-4760 alone worsened neurological function. The dynamic alterations of the protective angiotensin-converting enzyme 2 pathway after stroke suggest that it may be a favorable th...

Source: Hypertension - June 10, 2015 Category: Cardiology Authors: Bennion, D. M., Haltigan, E. A., Irwin, A. J., Donnangelo, L. L., Regenhardt, R. W., Pioquinto, D. J., Purich, D. L., Sumners, C. Tags: ACE/Angiotension receptors, Animal models of human disease, Other Treatment, Acute Cerebral Infarction, Neuroprotectors Renin-Angiotensin System Source Type: research