RESUMO
Angiotensin II [Ang II] has an important role on cerebral microcirculation; however, its direct roles in terms of ischemic brain edema need to be clarified. This study evaluated the role of central Ang II by using candesartan, as an ATI receptor blocker, in the brain edema formation and blood-brain barrier [BBB] disruption caused by ischemia/reperfusion [I/R] injuries in rat. Rats were exposed to 60-min middle cerebral artery [MCA] occlusion. Vehicle and non-hypotensive doses of candesartan [0.1 mg/kg] were administered one hour before ischemia. Neurological dysfunction scoring was evaluated following 24 h of reperfusion. Animals were then decapitated under deep anesthesia for the assessments of cerebral infarct size, edema formation, and BBB permeability. The outcomes of 24 h reperfusion after 60-min MCA occlusion were severe neurological disability, massive BBB disruption [Evans blue extravasation = 12.5 +/- 1.94 microg/g tissue], 4.02% edema, and cerebral infarction [317 + 21 mm[3]]. Candesartan at a dose of 0.1 mg/kg, without changing arterial blood pressure, improved neurological dysfunction scoring together with significant reductions in BBB disruption [54.9%], edema [59.2%], and cerebral infarction [54.9%]. Inactivation of central ATI receptors, if not accompanied with arterial hypotension, protected cerebral micro-vasculatures from damaging effects of acute stroke
RESUMO
Central renin angiotensin system has an important role on the cerebral microcirculation and metabolism. Our previous work showed that inhibition of angiotensin converting enzyme [ACE] activity prior to induction of ischemia protected the brain from severe ischemia/reperfusion [I/R] injuries. This study evaluated the impacts of post-ischemic inhibition of ACE, enalapril, on brain infarction in normotensive rats. Rats were anesthetized with chloral hydrate [400 mg/kg]. Focal cerebral ischemia was induced by 60-min intraluminal occlusion of right middle cerebral artery [MCA]. Intraperitoneal injection of enalapril [0.03 or 0.1 mg/kg] was done after MCA reopening [reperfusion]. Neurological deficit score [NDS] was evaluated after 24 h and the animals randomly assigned for the assessments of infarction, absolute brain water content [ABWC] and index of brain edema. Severe impaired motor functions [NDS = 2.78 +/- 0.28], massive infarction [cortex = 214 +/- 19 mm[3], striatum = 86 +/- 5 mm[3]] and edema [ABWC = 83.1 +/- 0.46%] were observed in non-treated ischemic rats. Nonhypotensive dose of enalapril [0.03 mg/kg] significantly reduced NDS [1.5 +/- 0.22], infarction [cortex = 102 +/- 16 mm[3], striatum = 38 +/- 5 mm[3]] and edema [ABWC = 80.9 +/- 0.81%]. Enalapril at dose of 0.1 mg/kg significantly lowered arterial pressure could not improve NDS [2.0 +/- 0.45] and reduce infarction [cortex = 166 +/- 26 mm[3], striatum = 71 +/- 11 mm[3]]. Post-ischemic ACE inhibition in the normotensive rats without affecting arterial pressure protects the brain from reperfusion injuries; however, this beneficial action is masked by hypotension