Rho Kinase-Mediated Reduction in Cardiac Capillary Endothelial Cell Dimensions, In Situ, Against Flow.
OBJECTIVE
We previously showed that ischemia, induced by interrupting vascular flow, reduced cardiac capillary caliber. This was accomplished by a reduction in endothelial cell dimensions which was sensitive to Rho kinase (ROK) inhibition and stabilization of the actin cytoskeleton. Here, we investigated whether similar changes in endothelial cells, in situ, could be elicited in the presence of flow through the capillary bed.


METHODS
Langendorffs perfused rat hearts were subjected to vasoactive agents, ischemia, and reperfusion. Luminal and abluminal perimeters of capillary cross-sections and their areas were measured from electron micrographs to monitor changes in endothelial cell dimensions.


RESULTS
Histamine (100 microM) reduced capillary endothelial cell dimensions, in situ, without endothelial injury. While cross-sectional areas of endothelial cells were not altered by histamine, all other parameters measured were significantly reduced in comparison to controls. These changes were pre- vented by ROK inhibition.


CONCLUSIONS
Cardiac capillary endothelial cells, in situ, are able to change shape against continuous flow. One hundred (100) microM histamine induces morphometric changes in these endothelial cells, in situ, without cell damage. These cell-shape changes require ROK and mimic those observed following myocardial ischemia. Targeting the actomyosin contractile system may be useful in ameliorating effects of ischemia on the myocardium
Glyn
Matthew C
MC
Leukocyte Biology, National Heart and Lung Institute, Sir Alexander Fleming Building, South Kensington Campus, Imperial College London, London, UK. m.glyn@imperial.ac.uk
Lawrenson
John G
JG
Ward
Barbara J
BJ
Clark
Peter
P
D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000502:physiology; D003326:Coronary Circulation / Q000502:physiology*; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D009200:Myocardial Contraction / Q000502:physiology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D054460:rho-Associated Kinases / Q000378:metabolism*
D054460:rho-Associated Kinases