Reversal and protection against indomethacin-induced blood stasis and mucosal damage in the rat jejunum by a beta(3)-adrenoceptor agonist.

Background: In the rat, indomethacin causes jejunal villous shortening, mic rovascular distortion, and blood stasis prior to ulceration, The beta(3)-ad renoceptor agonist CL316,243 (CL) prevents both the early histological chan ges and ulceration, Aim: To test the hypothesis that the beta(3)-adrenoceptor agonist CL316,243 exerts its protective effect by prevention and/or reversal of blood flow c hanges in the rat jejunum exposed to indomethacin, Methods: In anaesthetized rats, jejunal villous blood flow was measured in surface capillaries using fluorescence microscopy, Stasis of superficial ca pillary blood flow was induced by combined topical and i.v. indomethacin (1 00 mu g/mL, 2.8 x 10(-4) M). To examine the effect of CL on blood stasis, C L was applied either i.v. (1 mg/kg) or luminally (100 mu g/mL, 2.5 x 10(-5) M) at the onset of stasis. Prophylactic protection was assessed by giving i.v. CL simultaneously with indomethacin, Results were compared with contro ls which received luminal saline applied at blood stasis, The effect of i.v . CL (1 mg/kg) alone, or luminal CL (100 mu g/mL) alone on basal villous bl ood flow was also examined. The small intestines were perfusion-fixed with 10% formol saline, and removed for histology, n = 5 for all groups. Results: Luminal CL given at stasis reversed indomethacin-induced stasis wi thin 10 min, whereas i.v. CL did not. Pretreatment with i.v. CL prevented t he onset of stasis, Basal blood flow was raised slightly only by luminal CL , Conclusion: The beta(3)-adrenoceptor agonist CL316,243 can protect against indomethacin-induced blood stasis in rat jejunal villi.