urotensin-i and Ischemia

Three structurally related peptides, ovine corticotropin-releasing factor, sauvagine, and urotensin I are selective mesenteric vasodilators in dogs. To assess the possible benefit of these peptides in nonocclusive mesenteric ischemia, they were compared with a nonselective vasodilator, sodium nitroprusside, in the anesthetized dog. Mesenteric blood flow was reduced by approximately 30%, without lowering of systemic arterial pressure, by either digoxin or pericardial tamponade. In the digoxin model, i.v. infusions of corticotropin-releasing factor, sauvagine, and urotensin I restored intestinal vascular resistance and mesenteric blood flow to control values, without causing a fall in systemic arterial blood pressure. In the tamponade model, only urotensin I was assessed, and it produced the same restoration of hemodynamic variables. On the other hand, in both models, i.v. infusions of nitroprusside, which were effective in correcting intestinal vascular resistance, produced a fall in arterial blood pressure (presumably because of systemic dilatation), which prevented restoration of mesenteric blood flow. Intestinal oxygen uptake was not altered by tamponade, but was reduced by 23% in the digoxin model, where it was restored to control values by both the peptides and nitroprusside. The increased oxygen extraction seen in both models was corrected by the peptides but not by nitroprusside, suggesting that nitroprusside may have a direct and offsetting metabolic effect on the gut.

Topics: Amphibian Proteins; Animals; Blood Pressure; Cardiac Tamponade; Corticotropin-Releasing Hormone; Digoxin; Diuresis; Dogs; Female; Ischemia; Male; Mesenteric Arteries; Mesenteric Veins; Nitroprusside; Peptide Hormones; Peptides; Splanchnic Circulation; Urotensins; Vascular Resistance; Vasodilator Agents

Topics: Acute Disease; Humans; Ischemia; Mesenteric Arteries; Papaverine; Urotensins; Vasodilator Agents

Acute nonocclusive mesenteric ischemia was produced in dogs anesthetized with pentobarbital by reversible pericardial tamponade, which reduced cardiac output and mesenteric blood flow by approximately 42% and 53%, respectively. Papaverine, infused into the cephalic (superior) mesenteric artery at an average dose of 100 micrograms/kg X min, was completely effective in restoring mesenteric blood flow and correcting altered intestinal oxygen kinetics. However, the same dose of papaverine given intravenously to other dogs was ineffective in correcting the deranged hemodynamics and oxygen kinetics. Larger doses of intravenous papaverine returned mesenteric blood flow toward control values but caused systemic arterial hypotension. In comparison, synthetic urotensin I, a highly selective mesenteric vasodilator peptide, produced results identical to those produced by intraarterial papaverine, even though it was given intravenously in small doses (average dose: 13 ng/kg . min). Moreover, it produced no systemic effects. These results suggest that intravenous urotensin I is as effective as intraarterial papaverine in a model of severe mesenteric ischemia, and that it should be examined for a possible clinical role in the treatment of acute mesenteric ischemia in humans.

Topics: Animals; Blood Pressure; Dogs; Female; Infusions, Intra-Arterial; Infusions, Parenteral; Ischemia; Male; Mesenteric Arteries; Papaverine; Peptides; Urotensins; Vasodilator Agents