Bradykinin- and sodium nitroprusside-induced increases in capillary tube haematocrit in mouse cremaster muscle are associated with impaired glycocalyx barrier properties.
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.
VanTeeffelen
Jurgen W G E
JW
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. j.vanteeffelen@fys.unimaas.nl
Constantinescu
Alina A
AA
Brands
Judith
J
Spaan
Jos A E
JA
Vink
Hans
H
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
D014665:Vasodilator Agents; D009599:Nitroprusside; D001920:Bradykinin