Vasoactive agents and production of thrombosis during intravascular coagulation. 3. Comparative effects of catecholamines.
Epinephrine (E), isoproterenol (I), and dopamine (D) were compared with norepinephrine (N) for production of microthrombi during thrombin-induced disseminated intravascular coagulation (DIC) in rabbits. Only catecholamines acting on alpha-adrenoreceptors produced glomerular capillary thrombosis (GCT) typical of the generalized Shwartzman reaction (GSR). Epinephrine produced GCT three times (P less than 0.05) less severe than that produced by N, but beta-blockade with propranolol (P) rendered E equal to N in potency. I and D reduced fibrinogen consumption produced by thrombin. I (0.5-0.66 microgram/kg/min), as opposed to D, prevented the GSR produced by endotoxin in the pregnant rat and the cortisone-sensitized rabbit, and P increased the severity of the GSR in the pregnant rat. Alpha-adrenergic blockade with dibenzyline prevented the GSR produced by endotoxin in rats, whether pregnant, diabetic, or having a unilateral ureteral occlusion, and the classic reaction in rabbits, but not that produced in renal-hypertensive rats. Simultaneous alpha + beta stimulations by E triggered coronary and hepatic microthrombi, which were prevented by P. It is concluded that beta-adrenergic stimulation, as opposed to D-adrenergic stimulation, counterbalances alpha-adrenergic effects occurring in endotoxemia, which are required for production of the GSR in most models. These studies stress the risks and benefits of beta-blockade and provide additional evidence for the role of vasoactive agents and microcirculatory changes on selection of target organs for production of microthrombi during DIC.
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002196:Capillaries / Q000473:pathology; D002395:Catecholamines / Q000494:pharmacology*; D004211:Disseminated Intravascular Coagulation / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D004298:Dopamine / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D007678:Kidney Glomerulus / Q000098:blood supply*; D008297:Male; D011247:Pregnancy; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D012790:Shwartzman Phenomenon / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D013917:Thrombin / Q000494:pharmacology; D013927:Thrombosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*
D002395:Catecholamines; D004731:Endotoxins; D011943:Receptors, Adrenergic, beta; D005340:Fibrinogen; D011433:Propranolol; D013917:Thrombin; D004298:Dopamine