Acute effect of substance P in immunologic vasculitis in the rat colon.
Substance P has been implicated as a neuronal mediator of inflammation in various inflammatory conditions. However, the exact role played by substance P in inflammatory bowel diseases or in experimental colonic vasculitis has not been clearly understood. In this study, we examined the effect of close superior mesenteric artery injection of substance P under prevailing inflammatory conditions induced by intravenous human albumin antialbumin immune complex followed by intracolonic perfusion of 2.5% formaldehyde in rats or intracolonic perfusion of 5% alcohol alone. The immune complex- and formaldehyde-treated rats showed severe microvascular changes such as microvascular plugging by red blood cells, endothelial breakage and extravasation of plasma proteins and red blood cells. The bolus injection of 10(-8) M substance P reduced extravasation of Evans blue dye by 50% and the tissue wet to dry ratio by 20% in immune complex- and formaldehyde-perfused rats. Myeloperoxidase activity was not changed. Substance P also significantly inhibited (44%) the extravasation in alcohol-perfused rats. Pretreatment of immune complex- and formaldehyde-treated rats with substance P antagonist reversed the effect of substance P. These findings suggest that the most immediate effect of substance P may be vasodilation and clearing of vascular plugs induced by immune complex and formaldehyde. This effect of substance P differs from its chronic effect, which causes vasodilation and extravasation.
Murthy
S N
SN
Krancer Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Philadelphia, PA 19102-1192.
DePace
D M
DM
Shah
R S
RS
Podell
R
R
D000208:Acute Disease; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003108:Colonic Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D014657:Vasculitis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects
D013373:Substance P