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

The effects of endothelin-l (ET-1) infusion on blood flow ((Q) over dot(G)) and O-2 uptake ((V) over dot 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 (Q) over dot(G) were measured, and O-2 extraction ratio (OERG) and Vote were calculated. ET-1 was infused (0.118 mu g.kg(-1).min(-1) ia) throughout the experiment. Ingroup 1 (n = 5), ETA receptors were blocked using BQ-123 (0.143 mg.kg(-1).min(-1) ia) followed by blockade of ETB receptors with BQ-788 (0.145 mg.kg(-1).min(-1) ia). The order of ETA and ETB receptor blockade was reversed in group 2 (n = 5). Ingroup I, the decrease in (Q) over dot(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) over dot(G), whereas addition of BQ-123 returned (Q) over dot(G) to a value not different from that with ET-I infusion alone. These data indicated that ET-l-induced vasoconstriction in the gut was mediated via ETA receptors and that this constriction was buffered by activation of ETB receptors. (V) over dot O-2G decreased in proportion to the decrease in (Q) over dot(G) with ET-1, decreased further with ET-1 plus ETB receptor blockade (group 2), and increased in proportion to the increases in (Q) over dot(G) with ETA receptor blockade (both groups). No changes in OERG occurred during ETA and ETB receptor antagonism in either group. This study is the first to demonstrate that a flow-limited decrease in gut (V) over dot O-2G occurred with infusion of ET-1 in gut vasculature. An intriguing and novel finding was that, during O-2 limitation, OERG was only 50% of that normally associated with ischemia in this tissue.