Nitric oxide modulates microvascular permeability.
We recently demonstrated that inhibitors of nitric oxide (NO) production cause a dramatic increase in leukocyte adherence and emigration in postcapillary venules. The objective of this study was to assess whether inhibition of NO production leads to vascular protein leakage and increased microvascular permeability in feline small intestine and to determine whether adherent leukocytes contribute to these responses. Whereas NG-nitro-L-arginine methyl ester (L-NAME) produced fivefold increases in microvascular fluid and protein fluxes, capillary pressure remained unchanged. In some experiments, venous pressure was elevated and the microvascular reflection coefficient for total proteins (sigma d) was estimated from lymph to plasma protein concentration ratio at high capillary filtration rates. L-NAME infusion increased 1 - sigma d (permeability index) from a control value of 0.21 +/- 0.02 to 0.41 +/- 0.07. All of the L-NAME-induced microvascular alterations were completely reversed by nitroprusside. Some animals were pretreated with a monoclonal antibody (MoAb IB4) directed against the leukocyte adhesion glycoprotein complex CD11/CD18. MoAb IB4 did not prevent the initial rise in vascular protein leakage but greatly attenuated the later (30-60 min) phase of enhanced vascular protein leakage. Local intra-arterial infusion of the NO synthesis inhibitor L-NAME (0.025 mumol.ml-1.min-1) produced a profound increase in leukocyte adhesion in postcapillary venules that was partly reversed by sodium nitroprusside administration (0.025 mumol.ml-1.min-1). These results suggest that inhibition of NO production by vascular endothelium leads to a reversible increase in microvascular protein efflux that is mediated by both leukocyte-dependent and -independent mechanisms.
Kubes
P
P
Department of Physiology, University of Calgary, Alberta, Canada.
Granger
D N
DN
D000818:Animals; D000911:Antibodies, Monoclonal; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001826:Body Fluids / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002415:Cats; D002448:Cell Adhesion / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism
D000911:Antibodies, Monoclonal; D011506:Proteins; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester