PAF-induced bowel necrosis. Effects of vasodilators.
Ischemic bowel necrosis in the rat is produced by injecting platelet-activating factor (PAF) intravenously. Since intestinal hypoperfusion is observed after PAF injection, we hypothesize that mesenteric vasoconstriction is the mechanism of bowel injury. We thus studied the effects of vasodilators in this model. We found that: (1) Phenoxybenzamine, prazosin, ICI 198615 (leukotriene antagonist) and PGE1 counteracted the PAF-induced mesenteric flow reduction and ameliorated the bowel injury. However, phenoxybenzamine and prazosin were relatively ineffective in correcting PAF-induced hypotension, showing that bowel injury can be prevented independently of the hypotensive state. (2) Nitroglycerin failed to prevent bowel injury, although it improved the mesenteric blood flow. Thus, in opposition to our initial hypothesis, correction of the mesenteric flow reduction induced by PAF does not always prevent intestineal necrosis. (3) Only phenoxybenzamine, prazosin, ICI 198615, and PGE1 ameliorated PAF-induced hemoconcentration and bowel injury. This suggests a correlation between vascular injury (expressed by "leaky" vessels and the consequent hemoconcentration) and bowel necrosis. (4) Although both nitroglycerin and hydralazine relax smooth muscle, hydralazine seemed to aggravate bowel necrosis. The mechanism remains unclear.
Zhang
C
C
Department of Pathology, Children's Memorial Hospital, Northwestern University Medical School, Chicago, Illinois 60614.
Hsueh
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W
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D006830:Hydralazine / Q000494:pharmacology; D007022:Hypotension / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy; D007191:Indazoles / Q000494:pharmacology; D007410:Intestinal Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007970:Leukopenia / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009336:Necrosis; D005996:Nitroglycerin / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000037:antagonists & inhibitors; D014665:Vasodilator Agents / Q000494:pharmacology*
D007191:Indazoles; D010972:Platelet Activating Factor; D013189:SRS-A; D014665:Vasodilator Agents; D010643:Phenoxybenzamine; C054217:ICI 198615; D006830:Hydralazine; D000527:Alprostadil; D005996:Nitroglycerin; D011224:Prazosin