Receptor-mediated vascular and metabolic actions of endothelin-1 in canine small intestine.

The effects of endothelin-1 (ET-1) infusion on blood flow (Q˙G) and O2 uptake (V˙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 andQ˙G were measured, and O2 extraction ratio (OERG) andV˙o 2Gwere calculated. ET-1 was infused (0.118 μg ⋅ kg-1 ⋅ min-1ia) throughout the experiment. In group 1 ( n = 5), ETA receptors were blocked using BQ-123 (0.143 mg ⋅ kg-1 ⋅ min-1ia) followed by blockade of ETBreceptors with BQ-788 (0.145 mg ⋅ kg-1 ⋅ min-1ia). The order of ETA and ETB receptor blockade was reversed in group 2( n = 5). In group 1, the decrease inQ˙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 decreasedQ˙G, whereas addition of BQ-123 returnedQ˙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 ETA receptors and that this constriction was buffered by activation of ETB receptors.V˙o 2Gdecreased in proportion to the decrease inQ˙G with ET-1, decreased further with ET-1 plus ETB receptor blockade ( group 2), and increased in proportion to the increases in Q˙Gwith ETA receptor blockade (both groups). No changes in OERGoccurred during ETA and ETB receptor antagonism in either group. This study is the first to demonstrate that a flow-limited decrease in gutV˙o 2Goccurred with infusion of ET-1 in gut vasculature. An intriguing and novel finding was that, during O2limitation, OERG was only 50% of that normally associated with ischemia in this tissue.