[Alterations in number of rabbit myocardial beta-adrenergic receptors in endotoxic shock: down regulation in hyperdynamic sepsis model and effects of cytokines administration].
We investigated alterations in myocardial beta- and beta 1-adrenergic receptor (BAR and B1AR) number during hyperdynamic state induced by endotoxin or cytokines. [METHODS] Twenty-nine Japanese White rabbits were divided into 2 groups. Hearts were removed 18 h after intraperitoneal administration of sterile saline (SAL) or E. coli endotoxin (LPS; 50 micrograms/kg) (Group E, n = 12), or 3 h after intravenous injection of SAL or cytokines (interleukin 1-beta; 5 micrograms/kg followed by 25 ng/kg/min for 2 h, or tumor necrosis factor; 5 micrograms/kg) (Group C, n = 17). BAR and B1AR numbers were determined in myocardial membranes from rabbit left ventricles with techniques of radioactive ligand binding study. We used [3H] dihydroalprenolol (3H-DHA) as radioactive ligand, and specific 3H-DHA binding to BARs was defined as the difference between the presence and the absence of 10 microM propranolol. B1AR number was assessed through the specific binding of 3H-DHA in the presence of ICI 118, 551 (5 x 10(-8) M), a highly selective beta 2-adrenergic receptor antagonist. In Group E, mean arterial blood pressure (MAP), heart rate (HR), and cardiac output (CO) (by thermodilution) were measured under pentobarbital sodium anesthesia before excision of hearts. [RESULTS] In Group E, CO was significantly (p less than 0.05) increased in rabbits injected with LPS (E-LPS) as compared with that in rabbits injected with SAL (E-SAL) (E-LPS; 0.75 +/- 0.02 l.min-1, E-SAL; 0.61 +/- 0.05 l.min-1, mean +/- SEM). MAP and HR were slightly decreased in E-LPS but not significantly. Maximum binding (Bmax) of 3H-DHA to BARs was significantly (p less than 0.05) decreased by 18% in myocardial membranes from E-LPS compared to E-SAL (E-LPS; 48.2 +/- 4.3 fmol/mg protein, E-SAL; 58.9 +/- 2.9 fmol/mg protein, mean +/- SEM). Similarly, Bmax of 3H-DHA to B1ARs was decreased by 18% in E-LPS, although no statistical significance was detected. In Group C, both BAR and B1 AR number was slightly, but not significantly decreased 3 h after administration of cytokines. [CONCLUSION] These data suggest that down regulation of cardiac BARs may occur during hyperdynamic stage of endotoxic shock.
Yahagi
M
M
Department of Anesthesiology, Teikyo University School of Medicine.
Honda
T
T
Mizumachi
K
K
Tezuka
S
S
Okada
K
K
D000818:Animals; D002395:Catecholamines / Q000378:metabolism / Q000502:physiology; D004195:Disease Models, Animal; D015536:Down-Regulation; D004927:Escherichia coli Infections / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012772:Shock, Septic / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002395:Catecholamines; D007375:Interleukin-1; D011943:Receptors, Adrenergic, beta; D014409:Tumor Necrosis Factor-alpha