Abstract P159: Effect of Pharmacological Kinin Receptor Activation on Brain Damage and Mortality in Experimental Cerebral Ischemia in Non-diabetic and Diabetic Mice [Session Title: Cerebrovascular Disease and Stroke]

Brain ischemia is a major complication of arterial diseases and has a poorer prognosis in diabetic patients. As activation of the kallikrein-kinin system has been shown to enhance cardiac and renal tolerance to ischemia we tested effect of kinin receptor activation by pharmacological agonists, selective B1R or B2R, in a mouse model of transient middle cerebral artery occlusion [C57bl6 male, 10 week-old, anaesthesia, occlusion 60 min (MCAO)]. Treatment with the B1R agonist NG29 (B1Rago) or the B2R agonist NG291 (B2Rago) was started at reperfusion using osmotic micropumps. Neurological deficit (ND) was evaluated at 1 and 2 days using a panel of 8 established tests combined in a 0-30 deficit score. Brain infarction was quantified at day 2 using TTC and hematoxylin-eosin staining. In some mice diabetes was induced by streptozotocin 8 weeks before MCAO.MCAO induced bradychardia, mild hypotension (mean -11.3 mmHg), ND (19.7 ± 2.4) and resulted in partial brain infarction (18 ± 1.4 %), all p<0.05 compared to sham, n=10/group. B2Rago (720 nmol/kg.day-1) increased ND to 27 ± 1.8 at day 1 and mortality to 60% at day 2 (both p<0.05, n=10) while decreasing brain infarct size by 66% (p<0.01). B2Rago reduced BP by 16 mmHg and increased plasma creatinine (73 ± 25 μmol/l, p<0.05). Although B1R mRNA level increased by 1.3 fold in the ischemic brain B1Rago had no effect on ND, mortality or brain infarction.In diabetic mice MCAO increased ND (28 &plusm...
Source: Hypertension - Category: Cardiology Authors: Tags: Session Title: Cerebrovascular Disease and Stroke Source Type: research