Vasoactive agents and production of thrombosis during intravascular coagulation. 2. alpha-Adrenergic stimulation: effects and mechanisms.
The mechanism whereby norepinephrine elicits thrombosis during intravascular coagulation was investigated further in rabbits given a 4 h infusion of thrombin (1 NIH unit/kg/min). Norepinephrine (3 micrograms/kg/min) combined with thrombin produced glomerular capillary thrombosis in all animals as compared to 4.3% with thrombin alone. Alpha-adrenergic receptors mediated this effect, as indicated (a) by prevention of glomerular thrombosis by dibenzyline but not by methysergide, and (b) by failure of histamine or acetylcholine combined with thrombin to induce the phenomenon. However, in combination with thrombin, these two agents induced duodenal mucosal microthrombosis. Study of the glomerular circulation with colloidal carbon showed that norepinephrine elicits severe glomerular capillary stasis in thrombin treated rabbits; the vasomotor reaction precedes increased fibrinogen consumption and focal deposition of fibrin in the glomeruli. Pretreatment with dibenzyline prevented glomerular stasis and reduced fibrinogen consumption. The phagocytic activity of the reticulo-endothelial system was increased 7 times by thrombin infusions, with or without norepinephrine. We conclude that stimulation of the alpha 1-adrenergic receptors triggers glomerular thrombosis by production of severe glomerular stasis which localizes formation of thrombi in the dilated vessels. These results provide a rational explanation for the role of alpha-adrenergic stimulation in the endotoxin-induced generalized Shwartzman reaction and outline some of the mechanisms and agents implied in the selection of the target organs for thrombosis during intravascular coagulation.
D000818:Animals; D001792:Blood Platelets; D001794:Blood Pressure / Q000187:drug effects; D004903:Erythrocyte Aggregation / Q000139:chemically induced* / Q000473:pathology; D005340:Fibrinogen / Q000378:metabolism; D006098:Granulocytes / Q000502:physiology; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D009638:Norepinephrine; D011817:Rabbits; D012079:Renal Circulation; D013917:Thrombin / Q000494:pharmacology; D013927:Thrombosis / Q000139:chemically induced*
D005340:Fibrinogen; D013917:Thrombin; D009638:Norepinephrine