title: Bradykinin- and sodium nitroprusside-induced increases in capillary tube haematocrit in mouse cremaster muscle are associated with impaired glycocalyx barrier properties.
abstract: Previous studies have suggested that agonists may increase functionally perfused capillary volume by modulation of blood-excluding glycocalyx volume, but direct evidence for this association is lacking at the moment. Using intravital microscopic visualization of mouse cremaster muscle, we determined the effects of bradykinin (10(-5) M) and sodium nitroprusside (10(-6) M) on capillary tube haematocrit and glycocalyx barrier properties. In control C57Bl/6 mice (n = 10), tube haematocrit in capillaries (n = 71) increased (P < 0.05) from 8.7 +/- 0.3% during baseline to 21.2 +/- 1.2 and 22.2 +/- 0.9% during superfusion with bradykinin and nitroprusside, respectively. In parallel, the exclusion zone of FITC-labelled 70 kDa dextrans decreased (P < 0.05) from 0.37 +/- 0.01 microm during baseline to 0.17 +/- 0.01 microm with bradykinin and 0.15 +/- 0.01 microm with nitroprusside. Bradykinin and nitroprusside had no effect on dextran exclusion and tube haematocrit in capillaries (n = 55) of hyperlipidemic ApoE3-Leiden mice, which showed impaired exclusion of 70 kDa dextrans (0.05 +/- 0.02 microm; P < 0.05 versus C57Bl/6) and increased capillary tube haematocrit (23 +/- 0.8%; P < 0.05 versus C57Bl/6) under baseline conditions, indicating glycocalyx degradation. Our data show that vasodilator substances increase functionally perfused capillary volume and that this effect is associated with a reduction in glycocalyx exclusion of 70 kDa dextrans. Modulation of glycocalyx volume might represent a novel mechanism of perfusion control at the capillary level.
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. j.vanteeffelen@fys.unimaas.nl
authors.forename: Jurgen W G E
authors.initials: JW
authors.lastname: VanTeeffelen
authors.forename: Alina A
authors.initials: AA
authors.lastname: Constantinescu
authors.forename: Judith
authors.initials: J
authors.lastname: Brands
authors.forename: Jos A E
authors.initials: JA
authors.lastname: Spaan
authors.forename: Hans
authors.initials: H
authors.lastname: Vink
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects* / Q000502:physiology; D019276:Glycocalyx / Q000378:metabolism*; D006400:Hematocrit; D006949:Hyperlipidemias / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018715:Microscopy, Video; D018482:Muscle, Skeletal / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology*; D010539:Permeability; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; D001920:Bradykinin