Angiotensin II is the big culprit here. Let's discuss angiotensin II and what we can do to help our patients. Well, it has been known for many years that angiotensin II has a major impact on vascular disease and injury. Now, we're just starting to understand some of the specific actions of angiotensin II on the macrovascular and microvascular disease associated with diabetes. Of course, macrovascular disease implies accelerated atherosclerosis.
Microvascular disease is important in terms of diabetic retinopathy and diabetic nephropathy.
We know that angiotensin II is a major vasoconstrictor. Angiotensin II also promotes growth and remodeling of the vasculature and causes the remodeling associated with hypertension. Recently, Dave Harrison and colleagues at Emory have shown that angiotensin II, stimulates superoxide production and increases peroxynitrate anions and other oxygen-free radicals that damage tissues and decrease nitric oxide activity. So, there is a growing list of changes that promote atherosclerosis when angiotensin II levels are high. Well, certainly ACE inhibition is designed to impair angiotensin I to angiotensin II conversion, and therefore to decrease angiotensin II production.