Receptor-mediated vascular and metabolic actions of endothelin-1 in canine small intestine. Am. J. Physiol. 276 (Gastrointest. Liver Physiol. 39): G1131-G1136, 1999.-The effects of endothelin-1 (ET-1) infusion on blood flow (Q G ) and O 2 uptake (V O 2G ) were examined in the small intestine of anesthetized dogs (n ϭ 10). Arterial and venous flows of a gut segment were isolated, and the segment was perfused at constant pressure. Arterial and gut venous blood samples were taken, gut perfusion

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... ssure and Q G were measured, and O 2 extraction ratio (OER G ) and V O 2G were calculated. ET-1 was infused (0.118 µg · kg Ϫ1 ·min Ϫ1 ia) throughout the experiment. In group 1 (n ϭ 5), ET A receptors were blocked using BQ-123 (0.143 mg · kg Ϫ1 ·min Ϫ1 ia) followed by blockade of ET B receptors with BQ-788 (0.145 mg · kg Ϫ1 ·min Ϫ1 ia). The order of ET A and ET B receptor blockade was reversed in group 2 (n ϭ 5). In group 1, the decrease in Q G observed with ET-1 infusion was partially reversed with BQ-123; no further change occurred after BQ-788 administration. In group 2, addition of BQ-788 to the infusate further decreased Q G , whereas addition of BQ-123 returned Q G to a value not different from that with ET-1 infusion alone. These data indicated that ET-1-induced vasoconstriction in the gut was mediated via ET A receptors and that this constriction was buffered by activation of ET B receptors. V O 2G decreased in proportion to the decrease in Q G with ET-1, decreased further with ET-1 plus ET B receptor blockade (group 2), and increased in proportion to the increases in Q G with ET A receptor blockade (both groups). No changes in OER G occurred during ET A and ET B receptor antagonism in either group. This study is the first to demonstrate that a flowlimited decrease in gut V O 2G occurred with infusion of ET-1 in gut vasculature. An intriguing and novel finding was that, during O 2 limitation, OER G was only 50% of that normally associated with ischemia in this tissue. oxygen uptake; flow limitation; oxygen extraction THE EXPECTED VASCULAR response to infusion of endothelin-1 (ET-1) is a transient dilation that occurs over 30-60 s followed by a prolonged constriction; the maximal constrictor response is normally observed by 15 min but varies somewhat between tissues (19, 28, 33).