DESENSITIZATION OF RAT CARDIOMYOCYTE ADENYLYL-CYCLASE STIMULATION BY PLASMA OF NORADRENALINE-TREATED PATIENTS WITH SEPTIC SHOCK

The purpose of this study was to test the possibility that the mechani sms of catecholamine-induced desensitization of cardiac beta-adrenocep tor stimulation are modified in septic shock. Exposure of neonatal rat cardiomyocytes for 48 hr to plasma of noradrenaline-treated patients with septic shock led to a down-regulation of beta-adrenoceptors by 35 %, an increase in the level of inhibitory G protein alpha-subunits by 60%, and a decrease in isoproterenol-stimulated adenylyl cyclase activ ity by 50% in membranes prepared from the rat cardiomyocytes. Similar alterations were observed following pretreatment of the cells with pla sma of adrenaline-treated patients with cardiogenic shock. In contrast , exposure of the cardiomyocytes to plasma of intensive care patients without shock, and to plasma of dopamine-treated patients with septic shock did not induce alterations of the cardiomyocyte adenylyl cyclase system. The dosage of the catecholamines had to be increased within t he first two days of treatment in the noradrenaline-treated patients, but not in the dopamine-treated patients with septic shock. Thus, this observed tolerance to noradrenaline in the treatment of septic shock may, in part, be due to a desensitization of cardiac beta-adrenoceptor stimulation induced by the beta-adrenoceptor stimulatory effect of no radrenaline. (C) 1993 Wiley-Liss, Inc.