Pancreas-specific venular labeling by monastral blue B in the BB rat: modulation by prostaglandins and their inhibitors.
Leaky blood vessels in the microcirculation can be detected in vivo by injecting an animal with colloidal pigments like Monastral blue B (MbB). We have previously used this labeling method in the BB rat, an animal model of spontaneous autoimmune diabetes, and detected increased vascular permeability restricted to the venules of the pancreas. The earlier data suggested that pancreata of animals susceptible to labeling contain trapped intravascular monocytes that are activated to release vasoactive mediators after phagocytosis of MbB. To explore these observations further, we investigated the effects of prostaglandins on this system. Prostaglandins are known to be important mediators of inflammatory responses and to modulate the expression of disease in other animal models of autoimmunity. We now report that MbB-induced pancreatic labeling is modulated by misoprostol (an analogue of prostaglandin E1), prostaglandins of the E series, and inhibitors of prostaglandin synthesis. The nonsteroidal anti-inflammatory drugs ibuprofen and ketorolac both reduced the intensity of labeling in susceptible BB rats in a dose dependent manner. In contrast, both misoprostol and prostaglandin E2 given at low doses induced pancreatic permeability in the labeling-resistant Wistar Furth rat. To extend this finding, we also tested much higher drug doses, since at high concentrations, E series prostanoids exert anti-inflammatory effects. We observed that large doses of prostaglandin E1, prostaglandin E2, and misoprostol all suppressed labeling in the BB rat. We conclude that presence of MbB in the pancreatic circulation of the rat induces organ specific venular leakage by an inflammatory process involving prostaglandins.
Kitagawa
Y
Y
Department of Medicine, University of Massachusetts Medical School, Worcester 01605.
Desemone
J
J
Mordes
J P
JP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D004396:Coloring Agents; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D007052:Ibuprofen / Q000494:pharmacology; D007211:Indoles; D020910:Ketorolac; D016595:Misoprostol / Q000494:pharmacology; D009942:Organometallic Compounds; D010179:Pancreas / Q000098:blood supply*; D011453:Prostaglandins / Q000502:physiology*; D011458:Prostaglandins E / Q000502:physiology; D051381:Rats; D011913:Rats, Inbred BB; D011920:Rats, Inbred WF; D014046:Tolmetin / Q000031:analogs & derivatives / Q000494:pharmacology; D014699:Venules / Q000187:drug effects / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004396:Coloring Agents; D007211:Indoles; D009942:Organometallic Compounds; D011453:Prostaglandins; D011458:Prostaglandins E; D016595:Misoprostol; C015445:copper phthalocyanine; D014046:Tolmetin; D007052:Ibuprofen; D020910:Ketorolac