Inhibition of Rho kinase decreases hydraulic and protein microvascular permeability in cat skeletal muscle.
Rho-associated kinases are involved in regulation of actin-myosin contractility and the organization of the actin cytoskeleton in both endothelial and smooth muscle cells. By influencing the contraction of the intraendothelial filaments, Rho kinases may affect the size of the interendothelial gaps and thereby influence microvascular permeability. The aim of the study was therefore to investigate whether Rho kinases influence hydraulic and protein microvascular permeability. The study was performed on the autoperfused cat skeletal muscle. A capillary filtration coefficient (CFC) technique was used to evaluate changes in hydraulic permeability, and protein permeability was evaluated by estimation of the change in the reflection coefficient for albumin. In the first part of each experiment, the effects on CFC of three doses of the Rho kinase inhibitor Y-27632 of about 0.35, 0.70, and 1.05 microg/h per ml plasma flow were determined. There was a reduction in CFC at the lowest dose, and a tendency to further reduction at the higher doses used, reaching a decrease in CFC of 20%. The effects on CFC of the high and the middle dose did not differ. The reflection coefficient for albumin was increased by 31% following infusion of the highest dose of Y-27632. We conclude that hydraulic and protein microvascular permeability increase by Rho kinase activation, and that Rho kinase is involved in regulation of microvascular permeability.
Lundblad
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Department of Physiological Sciences, University of Lund, Sweden. cornelia.lundblad@mphy.lu.se
Bentzer
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Grände
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D000577:Amides / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000201:enzymology*; D010477:Perfusion; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D012709:Serum Albumin / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D054460:rho-Associated Kinases
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D011725:Pyridines; D012709:Serum Albumin; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases