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Candesartan attenuates ischemic brain edema and protects the blood-brain barrier integrity from ischemia/reperfusion injury in rats.

Panahpour H, Nekooeian AA, Dehghani GA - Iran. Biomed. J. (2014)

Bottom Line: Rats were exposed to 60-min middle cerebral artery (MCA) occlusion.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 AT1 receptors, if not accompanied with arterial hypotension, protected cerebral micro-vasculatures from damaging effects of acute stroke.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Physiology and Pharmacology, Medical School, Ardabil University of Medical Sciences, Ardabil, Iran. h.panahpour@arums.ac.ir.

ABSTRACT

Background: 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 AT1 receptor blocker, in the brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia/reperfusion (I/R) injuries in rat.

Methods: 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.

Results: 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 µg/g tissue), 4.02% edema, and cerebral infarction (317 ± 21 mm3). 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%).

Conclusions: Inactivation of central AT1 receptors, if not accompanied with arterial hypotension, protected cerebral micro-vasculatures from damaging effects of acute stroke.

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Related in: MedlinePlus

Mean arterial pressure (MAP) in sham-operated rats, vehicle-treated control, and 0.1 mg/kg candesartan-treated ischemic rats at 10 minutes before middle cerebral artery occlusion (MCAO), 30 minutes after MCAO, and 10 minutes after the beginning of reperfusion (n = 8). MCAO, Middle cerebral artery occlusion
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Figure 1: Mean arterial pressure (MAP) in sham-operated rats, vehicle-treated control, and 0.1 mg/kg candesartan-treated ischemic rats at 10 minutes before middle cerebral artery occlusion (MCAO), 30 minutes after MCAO, and 10 minutes after the beginning of reperfusion (n = 8). MCAO, Middle cerebral artery occlusion

Mentions: Mean arterial blood pressure. The results of blood pressure recordings indicated that mean arterial blood pressure of control ischemia and candesartan-treated rats were all in normal physiological range, and quantitatively no significant differences existed among them before, during, and after MCA occlusion (mean ± SEM, 92 ± 3 vs. 79 ± 2.9, 94 ± 1.6 vs. 83 ± 2.7, and 89 ± 3.5 vs. 77 ± 3.9, respectively, Fig. 1).


Candesartan attenuates ischemic brain edema and protects the blood-brain barrier integrity from ischemia/reperfusion injury in rats.

Panahpour H, Nekooeian AA, Dehghani GA - Iran. Biomed. J. (2014)

Mean arterial pressure (MAP) in sham-operated rats, vehicle-treated control, and 0.1 mg/kg candesartan-treated ischemic rats at 10 minutes before middle cerebral artery occlusion (MCAO), 30 minutes after MCAO, and 10 minutes after the beginning of reperfusion (n = 8). MCAO, Middle cerebral artery occlusion
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4225063&req=5

Figure 1: Mean arterial pressure (MAP) in sham-operated rats, vehicle-treated control, and 0.1 mg/kg candesartan-treated ischemic rats at 10 minutes before middle cerebral artery occlusion (MCAO), 30 minutes after MCAO, and 10 minutes after the beginning of reperfusion (n = 8). MCAO, Middle cerebral artery occlusion
Mentions: Mean arterial blood pressure. The results of blood pressure recordings indicated that mean arterial blood pressure of control ischemia and candesartan-treated rats were all in normal physiological range, and quantitatively no significant differences existed among them before, during, and after MCA occlusion (mean ± SEM, 92 ± 3 vs. 79 ± 2.9, 94 ± 1.6 vs. 83 ± 2.7, and 89 ± 3.5 vs. 77 ± 3.9, respectively, Fig. 1).

Bottom Line: Rats were exposed to 60-min middle cerebral artery (MCA) occlusion.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 AT1 receptors, if not accompanied with arterial hypotension, protected cerebral micro-vasculatures from damaging effects of acute stroke.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Physiology and Pharmacology, Medical School, Ardabil University of Medical Sciences, Ardabil, Iran. h.panahpour@arums.ac.ir.

ABSTRACT

Background: 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 AT1 receptor blocker, in the brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia/reperfusion (I/R) injuries in rat.

Methods: 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.

Results: 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 µg/g tissue), 4.02% edema, and cerebral infarction (317 ± 21 mm3). 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%).

Conclusions: Inactivation of central AT1 receptors, if not accompanied with arterial hypotension, protected cerebral micro-vasculatures from damaging effects of acute stroke.

Show MeSH
Related in: MedlinePlus