Mechanisms of Increased Infarct Volume in a Rat Model of Ischemic Stroke: Implications for Leptomeningeal Collateral Artery Function and Beta Blocker Therapy

Abstract

Beta blockers are associated with higher ischemic stroke risk than other anti-hypertensive medications, but the mechanisms of this increased risk remain unknown. We previously reported β1-adrenoceptor-mediated dilation of rat cerebral arteries that is inhibited by the clinical beta blocker metoprolol. The present study examines the effect of β1-adrenoceptor blockade on the leptomeningeal collateral arteries (LCAs). LCAs connect distal branches of middle cerebral arteries to those of posterior and anterior cerebral arteries and provide a path for protective retrograde blood flow to the ischemic tissue during stroke. Pre-treatment with metoprolol increased cerebral infarct volume in Sprague-Dawley rats after middle cerebral artery occlusion (MCAO). Recovery of cortical blood flow after acute MCAO estimated by laser speckle contrast imaging was significantly blunted by topical suffusion of CGP20712, a β1-adrenoceptor antagonist. Isolated LCAs constricted significantly to the mixed adrenoreceptor agonist norepinephrine after pre-treatment with CGP20712 during ex vivo pressure myography. The in vivo diameter response of LCAs or small pial resistance arterioles following MCAO, however, was not significantly altered by topical suffusion of CGP20712. More research is required to fully characterize the effects of beta blockers on cerebral arteries during ischemic stroke.