The effects of endothelin-1 (ET-1) infusion on blood flow (_G) and O₂ uptake (O_2G) were examined in the small intestine of anesthetized dogs (n = 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 pressure and _G were measured, and O₂ extraction ratio (OER_G) and O_2G were calculated. ET-1 was infused (0.118 µg · kg¹ · min¹ ia) throughout the experiment. In group 1 (n = 5), ET_A receptors were blocked using BQ-123 (0.143 mg · kg¹ · min¹ ia) followed by blockade of ET_B receptors with BQ-788 (0.145 mg · kg¹ · min¹ ia). The order of ET_A and ET_B receptor blockade was reversed in group 2 (n = 5). In group 1, the decrease in _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 _G, whereas addition of BQ-123 returned _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. O_2G decreased in proportion to the decrease in _G with ET-1, decreased further with ET-1 plus ET_B receptor blockade (group 2), and increased in proportion to the increases in _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 flow-limited decrease in gut O_2G occurred with infusion of ET-1 in gut vasculature. An intriguing and novel finding was that, during O₂ limitation, OER_G was only 50% of that normally associated with ischemia in this tissue.

oxygen uptake; flow limitation; oxygen extraction