Hypersensitive prostaglandin and thromboxane response to hormones in rabbit colitis.
Inflammation of the colon is associated with increased production of prostaglandins (PG) and thromboxanes (Tx), and these eicosanoids may contribute to the inflammatory, secretory, and motility dysfunctions in colitis. To evaluate the potential role of peptide hormones in the enhanced eicosanoid release, colitis was established in rabbits by a delayed-type hypersensitivity reaction to dinitrochlorobenzene and by an immune-complex-mediated reaction. PG and Tx were identified in the venous effluent of isolated perfused colons by radiochromatography after [14C]arachidonic acid prelabeling, as well as by bioassay, and then quantitated by immunoassay. The two colitis models were morphologically similar. Basal release of PGE2, PGI2, and TxA2 was two- to threefold greater from colitis tissue than from control tissue. Bradykinin (BK) and angiotensin II (ANG II) increased release of 14C-labeled eicosanoids, whereas several gastrointestinal hormones had no effect. In control colons, BK and ANG II increased PGE2 and PGI2 release (by about 2-fold) but did not alter TxA2. In contrast, BK and ANG II markedly exaggerated the release of eicosanoids in colitis. BK increased TxA2 release with 10-ng bolus injections in colitis, but there was no response with up to 10-micrograms bolus injections in control colons. The BK-induced Tx release in colitis was associated with an increase in vascular resistance (measured as perfusion pressure). Infusion of the selective Tx inhibitors dazoxiben and OKY-046 reduced TxB2 release by 96% and blunted the transient rise in perfusion pressure (from 17 +/- 5 to 5 +/- 2 mmHg). Since BK and possibly ANG II are increased at sites of inflammation, the hypersensitive eicosanoid response to these peptides may augment the eicosanoid-mediated manifestations of colitis.
D000818:Animals; D002250:Carbon Radioisotopes; D003092:Colitis / Q000209:etiology / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D004137:Dinitrochlorobenzene; D004342:Drug Hypersensitivity / Q000150:complications / Q000378:metabolism*; D006728:Hormones / Q000494:pharmacology*; D008297:Male; D010477:Perfusion; D011312:Pressure; D011453:Prostaglandins / Q000378:metabolism*; D011817:Rabbits; D013931:Thromboxanes / Q000378:metabolism*
D002250:Carbon Radioisotopes; D004137:Dinitrochlorobenzene; D006728:Hormones; D011453:Prostaglandins; D013931:Thromboxanes