Role of nitric oxide scavenging in peripheral vasoconstrictor response to beta beta cross-linked hemoglobin.
Transfusion with many crosslinked hemoglobin solutions causes an increase in arterial pressure that may be mediated by scavenging of nitric oxide (NO). If so, we postulated that inhibiting synthesis of NO after hemoglobin transfusion would fail to cause vasoconstriction ordinarily seen with such inhibition. In pentobarbital anesthetized cats, we tested whether administration of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), produced peripheral vasoconstriction after isovolemic exchange transfusion with hemoglobin to the same extent as occurs with L-NAME infusion in time controls and in controls matched for reduced hematocrit (17%) with albumin transfusion. Bovine hemoglobin was treated aerobically with bis-(3,5-dibromosalicyl)fumarate to produce beta beta-81 lysine crosslinks. Hemoglobin exchange transfusion increased mean arterial blood pressure and there was no further increase after L-NAME. In contrast, L-NAME increased pressure in the time controls and albumin controls. Hemoglobin transfusion decreased intestinal and renal blood flow, and there was no further decrease after L-NAME. In contrast, L-NAME decreased intestinal and renal blood flow in time controls and albumin controls. With L-NAME pretreatment in a separate group of cats, there was little further increase in arterial pressure or visceral vasoconstriction after hemoglobin transfusion. We conclude that the increase in arterial blood pressure after isovolemic crosslinked hemoglobin transfusion is best explained by scavenging of NO in intestinal and renal vascular beds.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D002415:Cats; D005078:Exchange Transfusion, Whole Blood; D005260:Female; D016166:Free Radical Scavengers; D006454:Hemoglobins / Q000627:therapeutic use*; D046911:Macromolecular Substances; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
D016166:Free Radical Scavengers; D006454:Hemoglobins; D046911:Macromolecular Substances; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester