The brain possesses the same renin-angiotensin system (RAS) as the systemic circulation. Recent experimental studies have shown that the brain RAS plays an important role in
stroke and neuronal protection through its effector
peptide angiotensin (Ang) II. Ang II exerts its
stroke-protective effects through stimulation of Ang II type 2 (AT2) receptors.
Angiotensin receptor blockers (ARBs) exert a dual influence, which is important in their
stroke protective effects. They selectively block the Ang II type 1 (AT1) receptors, decreasing local vasoconstriction, and allow free Ang II to stimulate the unoccupied AT2 receptor and increase local vasodilation, resulting in the alleviation of local
brain ischemia and limiting the volume and extent of brain loss. In contrast,
angiotensin-converting enzyme (
ACE) inhibitors, by decreasing the amount of Ang II production, may diminish the
stroke-protective effects of Ang II. This perhaps could be a reason for the inferior
stroke-protective effect of
ACE inhibitors compared with ARBs, which has been demonstrated in several clinical trials. The evidence for this effect of ARBs compared with
ACE inhibitors, however, is only indirect. Ongoing clinical trials with head-to-head comparisons of ARBs and
ACE inhibitors will hopefully provide the needed information.