Nitric oxide: role in venular permeability recovery after histamine challenge.
Histamine is an inflammatory mediator produced by mast cells that reside close to blood vessels. It causes a transient increase in venular permeability and stimulates endothelial production of nitric oxide (NO). In this study, we investigated the role that NO plays in the permeability recovery and evaluated the response of mast cells. The mesenteric microvasculature of anesthetized rats was suffused with 10(-3) M histamine for 3 min and then perfused with the NO donor sodium nitroprusside (SNP; 10(-6) M), the NO inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 10(-5) M), its enantiomer (D-NMMA; 10(-5) M), or HEPES-buffered saline containing 0.5% BSA for 15 min. This was replaced by FITC-albumin for 3 min, followed by fixative. The vasculature was visualized using epifluorescence microscopy and was stained for mast cells. Preparations treated with histamine only showed discrete FITC-albumin leaks. Subsequent inhibition of NO increased venular FITC-albumin leaks and prevented permeability recovery, whereas subsequent treatment with SNP decreased the histamine-induced venular leaks. Mast cells degranulated due to histamine and the other treatment combinations. In conclusion, inhibition of NO prevented permeability recovery and depleted mast cells of their histamine content.
Al-Naemi
H
H
Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona 85724-5051, USA.
Baldwin
A L
AL
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology*; D015550:Cell Degranulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014699:Venules / Q000187:drug effects* / Q000378:metabolism*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D006632:Histamine