Angiotensin type 1 receptor blockage improves ischemic injury following transient focal cerebral ischemia.

Abstract

Following cerebral ischemia, i.v. infusion of angiotensin II increases cerebral edema and mortality. Angiotensin type 1 receptor blockage should therefore improve acute cerebral ischemia. Left middle cerebral artery occlusion (120 min) followed by reperfusion was performed with the thread method under halothane anesthesia in Sprague-Dawley rats. Olmesartan (angiotensin type 1 receptor blocker; 0.01 or 0.1mumol/kg/h) was infused i.p. for 7 days following middle cerebral artery occlusion followed by reperfusion. Stroke index score, infarct volume, specific gravity, and brain angiotensin II and matrix metalloproteinases were quantified in the ischemic and non-ischemic hemispheres. Olmesartan treatment improved stroke index score, infarct volume, and cerebral edema in our cerebral ischemia model. In particular, stroke index score, infarct volume, and cerebral edema were reduced even with a low dose of olmesartan that did not decrease blood pressure. Paralleling these effects on cerebral ischemia, olmesartan treatment also reduced the reactive upregulation in brain angiotensin II, matrix metalloproteinase-2, matrix metalloproteinase-9, and membrane type 1-matrix metalloproteinase in the ischemic area. Angiotensin type 1 receptor stimulation may be one of the important factors that cause cerebral edema following cerebral ischemia, and that its inhibition may be of therapeutic advantage in cerebral ischemia.

• Authors: N Hosomi, A Nishiyama, C R Ban, T Naya, T Takahashi, M Kohno, J A Koziol
• Journal: Neuroscience (Neuroscience) Vol. 134 Issue 1 Pg. 225-31 ( 2005) ISSN: 0306-4522 [Print] United States
• PMID: 15963646 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Imidazoles
• Neuroprotective Agents
• Receptor, Angiotensin, Type 1
• Tetrazoles
• Angiotensin II
• Olmesartan Medoxomil
• Matrix Metalloproteinases, Membrane-Associated
• Metalloendopeptidases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Analysis of Variance
• Angiotensin II (metabolism)
• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Animals
• Blood Pressure (drug effects)
• Brain (metabolism, pathology)
• Brain Edema (etiology, prevention & control)
• Brain Infarction (etiology, prevention & control)
• Dose-Response Relationship, Drug
• Imidazoles (therapeutic use)
• Ischemic Attack, Transient (complications, drug therapy)
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Matrix Metalloproteinases, Membrane-Associated
• Metalloendopeptidases (metabolism)
• Neurologic Examination
• Neuroprotective Agents (therapeutic use)
• Olmesartan Medoxomil
• Rats
• Rats, Sprague-Dawley
• Receptor, Angiotensin, Type 1 (physiology)
• Reperfusion
• Tetrazoles (therapeutic use)
• Time Factors