Neuroprotective effects of angiotensin II type 1 receptor blocker on intracerebral hemorrhage in spontaneously hypertensive rats

Abstract

Objective To investigate the neuroprotective effects ofangiotensin II type 1 receptor （AT1R） blocker olmesartan medoxomil （OLM） on intracerebral hemorrhage （1CH） in spontaneously hypertensive rats （SHRs）. Methods SHRs （male, 12 weeks old; weighing 300±20 g） were randomly assigned to normal, ICH, vehicle-treatment ICH （control）, OLM-treatment ICH （OLM） groups. ICH was induced via stereotaxic right basal ganglia administration ofcollagenase type Vii. One hour after ICH, the rats in OLM group were given a single oral dose of OLM （10 or 3 mg/kg solved in 1 mL sodium carboxymethylcellulose） via nasogastric feeding, and those in the control group received an equal volume of sodium carboxymethylcellulose only. Six hours after ICH induction, mean arterial blood pressure （MAP） was measured using the non-invasive method of tail-cuff plethysmography in conscious rats. Twenty-four hours after ICH induction, neurobehavior was detected by the modified limb placing test （MLPT）; brain water content was measured by dry-wet method; the mRNA expression levels of receptor and target genes were analyzed by real-time PCR. Results MAP in the ICH group （[121.4±3.5] mm Hg） did not significantly differ from baseline pressure in the normal group （[120.2±3.8] mm Hg）（P〉0.05）; MAP in the OLM group with 10 mg/kg （[105.6±3.1] mm Hg） was significantly lower than that in the ICH group （P〈0.05）; the OLM group with 3 mg/kg （[120.8±3.1] mm Hg） and control group （[118.6±3.9] mm Hg） did not induce blood pressure reduction, and did not show significant difference as compared with the ICH group （P〉0.05）. In the hemorrhagic hemisphere, brain water content in the OLM group with 3 mg/kg （80.02%±0.32%） had significant difference fi＇om that in the ICH group （80.90%±0.36%, P〈 0.05）; brain water content of the control group （80.81%±0.32%） was slightly lower than that of the ICH group, without significant differences （P〉0.05）. The OLM group with 3 mg/kg （5.03±0.71） was showed significantly lower score of MLPT as compared with that in the ICH group （6.62±0.55, P〈0.05）. The score of MLPT in the control group （6.41±0.55） did not differ from that in the ICH group （P〉0.05）. In the hemorrhagic hemisphere, the mRNA expressions of AT1R and target genes, such as HO-1, COX-2, IL-6 and VCAM-1, in the OLM group with 3 mg/kg were significantly lower than those in the ICH group （P〈0.05）, but the difference between the control and ICH groups did not show statistical significance （P〉0.05）. Conclusion Treatment with low doses of OLM in the experimental ICH of SHRs may promote its neurological recovery and induce its neuroprotective effects, including reduction of edema, inhibition of inflammation and oxidative stress. Key words: Angiotensin II; Receptor blocker; Spontaneously hypertension; Intracerebral hemorrhage