The pathophysiologic role of the brain renin-angiotensin system in stroke protection: clinical implications.
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.
Chrysant
Steven G
SG
University of Oklahoma School of Medicine and the Oklahoma Cardiovascular and Hypertension Center, Oklahoma City, OK 73132-4904, USA. schrysant@yahoo.com
D000804:Angiotensin II / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001794:Blood Pressure / Q000502:physiology; D006801:Humans; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*; D020521:Stroke / Q000503:physiopathology* / Q000517:prevention & control*; D014661:Vasoconstriction / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II