Mast cell degranulation in rat mesenteric venule: effects of L-NAME, methylene blue and ketotifen.
Mast cells are present in proximity to the microvessels, and on stimulation with inhibition of NO synthesis, are a rich source of numerous inflammatory mediators. A microcirculatory study was undertaken to clarify whether nitric oxide (NO) and activation of guanylate cyclase is involved in degranulation of perivascular mast cells in the rat mesenteric venule, and whether oral administration of ketotifen suppress the degranulation. Intravital microscopy was used to monitor the rates of adherence and extravasation of leukocytes in single unbranched venules with diameters between 25 and 35 microm of rat mesentery. Leukocyte rolling velocity, red blood cell velocity, vessel diameter and blood pressure were also measured. Mast cell degranulation was quantified within 30 microm from the venule. NG-nitro-L-arginine methyl ester (L-NAME) at an intravenous dose of 30 mg kg-1 increased the number of degranulated cells, while its enantiomer, D-NAME at the same dose had no effect. Superfusion with methylene blue (MB), an inhibitor of soluble guanylate cyclase, at 50 microm elicited similar degranulation of the mast cells. The degranulation was associated with increased adhesion of leukocytes to the endothelium and the slowed rolling. Pretreatment with ketotifen at an oral dose of 1 mg kg-1 inhibited mast cell degranulation in responses to either L-NAME or MB. It is conceivable that guanylate cyclase for NO production pathway in endothelial and/or mast cells is involved in the mast cell degranulation process, and the process or subsequent action of NO may be preserved by ketotifen, eliciting down-modulation of mast cell activation.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000502:physiology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D007665:Ketotifen / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D008751:Methylene Blue / Q000494:pharmacology*; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects*; D013237:Stereoisomerism; D014699:Venules