Receptor-mediated vascular and metabolic actions of endothelin-1 in canine small intestine.
The effects of endothelin-1 (ET-1) infusion on blood flow (QG) and O2 uptake (VO2G) 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 QG were measured, and O2 extraction ratio (OERG) and VO2G were calculated. ET-1 was infused (0.118 microgram. kg-1. min-1 ia) throughout the experiment. In group 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). In group 1, the decrease in QG 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 QG, whereas addition of BQ-123 returned QG 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. VO2G decreased in proportion to the decrease in QG with ET-1, decreased further with ET-1 plus ETB receptor blockade (group 2), and increased in proportion to the increases in QG 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 VO2G occurred with infusion of ET-1 in gut vasculature. An intriguing and novel finding was that, during O2 limitation, OERG was only 50% of that normally associated with ischemia in this tissue.
D000818:Animals; D001783:Blood Flow Velocity; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D007421:Intestine, Small / Q000098:blood supply* / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010101:Oxygen Consumption; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction