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Oral Metoprolol Attenuates Dilation of Leptomeningeal Collateral Arteries after Middle Cerebral Artery Occlusion and Increases Infarct Volume in Sprague Dawley Rats
Author(s) -
Henry David S.,
McClenahan Samantha J.,
Rusch Nancy J.,
Rhee Sung W.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.712.13
Subject(s) - medicine , metoprolol , stroke (engine) , agonist , middle cerebral artery , cardiology , anesthesia , receptor , ischemia , mechanical engineering , engineering
Background Beta‐adrenergic receptor antagonists, or beta blockers (BBs), have long been a mainstay in the treatment of hypertension, heart failure, and angina. In 2014, the Eighth Joint National Committee removed BBs from the list of recommended first‐line hypertension therapies, citing an increased incidence of stroke among patients treated with BBs compared to other antihypertensive medications. However, in 2015, more than 72 million prescriptions of this drug class were filled in the United States. The mechanism behind worse stroke outcomes in BB‐treated patients is unknown. Leptomeningeal collateral arteries (LCAs) connect adjacent arterial trees of the cerebral circulation, and after ischemic stroke, provide an alternative pathway for blood flow to the affected cortical tissue. We hypothesize that beta‐adrenergic receptor‐mediated dilation of LCAs is an important part of this protective mechanism during ischemic stroke and that BBs attenuate this dilation, leading to worse stroke outcomes. Methods and Results LCAs dilated in a concentration‐dependent manner to topical application of the beta‐adrenergic receptor agonist isoproterenol in cranial window preparations in Sprague Dawley (SD) rats. Isolated, pressurized LCAs dilated in response to isoproterenol ex vivo, and this dilation was attenuated by the beta1‐selective blocker CGP20712 (30 nM). LCAs acutely dilated after middle cerebral artery occlusion (MCAO) in SD rats. The dilation of LCAs after MCAO was reduced in rats suffused with topical CGP20712 (100 nM) or gavaged with oral metoprolol (30 mg/kg), the most frequently prescribed BB. Similarly, blood flow through LCAs post‐MCAO was reduced in rats gavaged with metoprolol compared to control rats, as visualized by laser speckle contrast imaging. Finally, infarct volume, as measured by MRI one day post‐MCAO surgery, was larger in rats gavaged with metoprolol compared to control. Interestingly, the heart rate and systemic blood pressure measured by biotelemetry for 6 hours following MCAO surgery were not different in rats gavaged with metoprolol and water. Conclusions Our study suggests that BBs may promote worse stroke outcomes by disrupting beta‐adrenergic receptor‐mediated dilation of LCAs. Support or Funding Information Supported by NIH R01 HL097107, American Heart Association 17GRNT33670970, and Institutional Hornick and Fund‐to‐Cure‐Stroke grants This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .