Hepatic alpha 1-adrenergic receptor alteration in a rat model of chronic sepsis.
Catecholamine therapy is often ineffective in reversing the peripheral vasodilatation and hypotension of septic shock. This suggests that catecholamines might not be able to activate alpha 1-adrenergic receptors to cause vasoconstriction. Despite elevations in endogenous catecholamines, hypoglycemia is also a complication of human sepsis, suggesting that among many other causes, hepatic alpha 1-receptors might be altered. To better understand the pathophysiologic basis for this pharmacologic dilemma, we studied the effect of experimental sepsis on alpha 1-adrenergic receptors in hepatic tissue, a rich source of alpha 1-receptors, from septic and control Sprague-Dawley rats. alpha 1-adrenergic receptors were measured with [3H]-prazosin and data analyzed by a computerized nonlinear least-square regression algorithm. Twenty-four hours following cecal ligation with puncture, a decreased number of alpha 1-adrenergic receptors was noted in crude and purified plasma membrane fractions (23 and 40% reductions respectively) from septic animals. No changes in either agonist or antagonist affinity for receptors from septic animals were noted. These data indicate that the catecholamine refractoriness seen in septic shock may be a result of alterations in alpha 1-adrenergic receptor number or receptor-effector coupling.
D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism*; D002908:Chronic Disease; D004088:Dihydroergotoxine / Q000378:metabolism; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000032:analysis*; D008297:Male; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000032:analysis*; D012772:Shock, Septic / Q000378:metabolism; D014316:Tritium
D011942:Receptors, Adrenergic, alpha; D014316:Tritium; D004088:Dihydroergotoxine; D006165:Guanylyl Imidodiphosphate; D005947:Glucose; D011224:Prazosin