Post-stroke losartan and captopril treatments arrest hemorrhagic expansion in SHRsp without lowering blood pressure

Abstract

We assessed the ability of poststroke losartan and captopril treatment to attenuate hematoma expansion and plasma extravasation after intracerebral hemorrhagic stroke in Kyoto-Wistar stroke-prone hypertensive rats (SHRsp). Cerebrum volume, herniation and surface areas exhibiting new and old hemorrhages and albumin extravasation were measured prior to and after stroke and following 30 and 60 days of post-stroke losartan or captopril treatment in Evans Blue dye perfused brains. Lesion morphology was studied in serial sections. Losartan or captopril treatment initiated at stroke prevented death for 60 days without lowering BP. Stroke onset was associated with the development and subsequent expansion of cerebrum volume, herniation, hematoma and plasma albumin extravasation. Losartan arrested cerebral volume expansion and herniation, and produced the virtual disappearance of hematoma and plasma albumin extravasation after 60 days. Captopril treatment equally attenuated cerebral herniation and hematoma expansion but was less effective in stopping albumin extravasation and allowed cerebrum volume to increase to post-stroke levels after 60 days of treatment. Both treatments resolved hematomas into cortical fluid filled spaces and prevented new hemorrhage formation. We believe that the treatments attenuated death after stroke by inhibiting hemorrhagic expansion through non-pressure related physiological changes mediated by the inhibition of the renin-angiotensin system.

Keywords: Angiotensin converting enzyme inhibitors; Angiotensin receptor blockers; Brain pathology; Edema; Hematoma; Hemorrhagic stroke; Hypertension; Post-stroke therapy; Renal function.