Differences in vascular response to thromboxane between intestinal mucosa and muscularis

The effects of a thromboxane A2 (TxA2)-endoperoxide analogue, U-44069 (0.16 micrograms/min. i.a.) on blood flows to the total wall, the mucosal (= mucosa+submucosa), and muscularis (= muscularis+serosa) layers of the canine jejunum, were determined utilizing radiolabelled microspheres (diam = 13.75 microns). U-44069 significantly decreased total (-64 +/- 5%), mucosal (-67 +/- 5%), and muscularis (-53 +/- 6%) blood flows in the natural flow preparation. In the constant flow preparation, U-44069 increased jejunal vascular resistance from 2.02 +/- 0.27 to 4.6 +/- 0.65 mmHg/ml/min/100g and increased mucosal and muscularis vascular resistance by 3.5-fold and 1.5-fold, respectively. As a result, it decreased mucosal blood flow (-19 +/- 5%), but increased muscularis blood flow (+52 +/- 10%). The magnitude of U-44069-induced percent change in mucosal blood flow was significantly different from that of the muscularis. Furthermore, U-44069 significantly redistributed the total jejunal blood flow in favor of the muscularis in both natural and constant flow preparations. Intra-arterial administration of a TxA2 receptor antagonist, SQ-29548 (2.0 micrograms i.a.) reversed all of the above U-44069-induced blood flow changes to control values. Our study indicates that TxA2 produces a significantly greater vasoconstriction in the mucosa than in the muscularis of the canine jejunum. This differential action of TxA2 may have some physiological and pathophysiological significance.