Misoprostol attenuates acetic acid-induced increases in mucosal permeability and inflammation: role of blood flow.
The objectives of this study were 1) to quantify the effects of misoprostol (Miso; prostaglandin E1 analogue) on acetic acid-induced increases in mucosal permeability and inflammation; 2) to determine what effect acetic acid, Miso, or the combination of Miso plus acetic acid has on colonic blood flow; and 3) to assess whether the protective effect of Miso may be attributable to its vasodilatory properties. We found that intrarectal administration of acetic acid produced a 6.4-fold increase in colonic myeloperoxidase activity (an index of granulocyte infiltration), an 8.2-fold increase in mucosal permeability, a 1.6-fold increase in colonic weight, and a 6.8% decrease in body weight 48 h after enema. Miso pretreatment significantly attenuated the increases in colonic myeloperoxidase activity, mucosal permeability, and colon weight as well as prevented the loss of body weight. In a different series of experiments, we found that blood flow in the descending, transverse, and ascending colon increased 2.5- to 3.5-fold immediately after the acetic acid enema; however, it returned to control values at 1 and 4 h after enema. Miso pretreatment, followed by acetic acid, resulted in a further increase (2.5-fold) in blood flow in the descending colon 1 h after enema compared with acetic acid alone. This Miso-induced increase in blood flow at 1 h could not account for its protective effect inasmuch as colonic mucosal permeability (i.e., injury) in Miso-pretreated animals was not significantly different from values obtained in animals pretreated with vehicle and then given the enema.
Yamada
T
T
Departments of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport 71130.
Specian
R D
RD
Granger
D N
DN
Gaginella
T S
TS
Grisham
M B
MB
D000085:Acetates / Q000494:pharmacology*; D019342:Acetic Acid; D000285:Administration, Rectal; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D003092:Colitis / Q000473:pathology* / Q000503:physiopathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D016595:Misoprostol; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects
D000085:Acetates; D000897:Anti-Ulcer Agents; D016595:Misoprostol; D000527:Alprostadil; D019342:Acetic Acid