Na+/H+ exchange inhibitor SM-20220 improves endothelial dysfunction induced by ischemia-reperfusion

Japanese Journal of Pharmacology
N HorikawaN Ohashi

Abstract

Endothelial cells play an important role in the physiologic homeostasis of the cerebral circulation. Previously, we showed that the Na+/H+ exchanger (NHE) inhibitor SM-20220 (N-(aminoimino-methyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate) improved ischemic brain injury. In this study, we investigated the effect of SM-20220 on cerebrovascular dysfunction after ischemia-reperfusion, focusing on the kinds of dysfunction that involved endothelial function. In cultured bovine brain microvascular endothelial cells (BBMCs), the IC50 value for the NHE activity of SM-20220 was 4 x 10(-8) M. SM-20220 also reduced the cell injury induced by hypoxia/aglycemia-reoxygenation in BBMCs, with statistical significance at 10(-7) M (P<0.05). Next, the effect of SM-20220 on disruption of the blood-brain barrier and cerebral blood flow were evaluated using transient middle cerebral artery (MCA) occlusion models. Intravenous infusion of SM-20220 (0.4 mg/kg per hour for 1 h) attenuated the extravasation of Evans blue, a blood-brain barrier disruption indicator, into cerebral tissue on the day after transient ischemia (P<0.05). The occlusion of the MCA decreased the cerebral blood flow in the MCA territory by about 20%, and only about 45% of t...Continue Reading

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Citations

Jan 24, 2014·Translational Stroke Research·Cristina Uria-Avellanal, Nicola J Robertson
Aug 18, 2004·Journal of Neurosurgery·Prajak SaesueKazuhiro Hongo
Nov 15, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Martha E O'DonnellSteven E Anderson
Jul 22, 2008·Neuropharmacology·Leif Hertz
Oct 27, 2007·Pathophysiology : the Official Journal of the International Society for Pathophysiology·Alexander A Mongin
Feb 1, 2005·The Annals of Thoracic Surgery·Manuel CastelláZhongtuo Tan
Jun 19, 2004·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·Martin ScholzAnton Moritz
Feb 18, 2006·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·S F PedersenP M Cala
Feb 12, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Kuniyuki NakamuraMitsuo Iida
May 29, 2015·Journal of Basic and Clinical Physiology and Pharmacology·Vivek VermaAmteshwar Singh Jaggi
Oct 13, 2017·Physiology·Shiren SunQi Qian

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