Endothelin B receptor-mediated increase of cerebral blood flow in experimental pneumococcal meningitis

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Uwe KoedelH-W Pfister

Abstract

Study investigates the role of endothelin (ET) receptors in mediating early changes in cerebral blood flow--as measured by laser Doppler flowmetry (CBFLDF)--during experimental pneumococcal meningitis. Meningitis was induced with heat-killed pneumococci and confirmed by a significant increase in CBFLDF (baseline 100%; 225.3 +/- 21.8% after 6 hours; mean +/- SD), intracranial pressure (ICP), brain water content, and white blood cell count in the CSF. Intravenous administration of the selective endothelin B (ETB) receptor antagonist BQ-788 immediately before pneumococcal challenge (but not 4 hours afterward) significantly attenuated these pathophysiologic alterations (e.g., CBFLDF 6 hours after pneumococcal challenge: 116.7 +/- 17.4%). Pretreatment with BQ-123, a selective endothelin A receptor antagonist, had no significant effect on ICP and brain water content, but augmented the increase in CBFLDF and CSF white blood cell count. Since ET is known to trigger the release of nitric oxide (NO) by ETB receptor activation, we examined specific ET-NO interactions in primary rat cerebromicrovascular endothelial cells after stimulation with heat-killed pneumococci. Pneumococci induced a significant increase in both ET and NO concentrati...Continue Reading

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Citations

Nov 30, 2000·Current Infectious Disease Reports·H W PfisterR Paul
Sep 2, 1999·Infectious Disease Clinics of North America·U Koedel, H W Pfister
Jul 17, 2007·Progress in Cardiovascular Diseases·Antonio Franco Folino
May 2, 2014·Life Sciences·Brandi D FreemanMahalia S Desruisseaux
May 3, 2016·Progress in Neurobiology·Stéphanie HostenbachJacques De Keyser
Dec 17, 2005·Journal of Applied Physiology·Jon AndresenRobert M Bryan

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