NOS3 and brain ischemia: In animal models, angiotensin-converting enzyme inhibitors (ACE-I) and AT1 receptor blockers (ARBs) are able to reduce eNOS uncoupling, while restoring BH4 bioavailability [98], and to protect against cerebral ischemia via upregulation of the eNOS in middle cerebral artery [99] and cerebral infarct size via eNOS activation [100].