Nitric oxide decreases microvascular permeability in bradykinin stimulated and nonstimulated conditions.
This study examined the occurrence of endothelial nitric oxide (NO)-synthase (NOS-III) in terminal mesenteric vessels and the involvement of NO in microvascular permeability. Possible effects were studied in bradykinin (BK)-induced and basal conditions. NOS expression was investigated by using NOS-III immunohistochemistry and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry on the light- and electron-microscopic levels. Permeability was examined in dissected mesenteries of male rats weighing 250-300 g. Tissue treatment was performed with BK (100 nM), sodium nitroprusside (SNP, 1 and 10 microM), L-nitroarginine (L-NA, 300 microM), BK and L-NA, BK and SNP, L-NA and SNP, as well as with BK, SNP (10 microM), and the guanylylcyclase inhibitor ODQ (10 microM), and BK and ODQ alone. Pharmacologically induced permeability changes were studied with fluorescein isothiocyanate (FITC)-dextran 70 kDa as a tracer for macromolecular transport. Video images were analyzed with computer determination of integrated optical density (IOI). Results were statistically verified by analysis of variance and t test. Microvascular permeability was increased by 168% after BK treatment and was enhanced by NO-synthesis inhibition with L-NA by 607%. However, the NO donor SNP led to a reduced tracer extravasation to 105 and 58%, respectively, an effect blocked by ODQ. Under basal conditions without prior BK induction, L-NA also causes an increase of IOI by 25%, whereas coapplication with SNP resulted in only a 10% increase of permeability. These results point out that NO has a modulatory role for microvascular permeability by supporting the barrier function of the endothelial lining in stimulated and nonstimulated conditions.
Arnhold
S
S
Department of Anatomy, University of Cologne, Köln, Germany.
Antoine
D
D
Bläser
H
H
Bloch
W
W
Andressen
C
C
Addicks
K
K
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D004347:Drug Interactions; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008643:Mesentery / Q000187:drug effects / Q000473:pathology; D008854:Microscopy, Electron; D009252:NADPH Dehydrogenase / Q000032:analysis; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase; D001920:Bradykinin