THE EFFECTS OF ALPHA-ADRENERGIC BLOCKADE ON ARACHIDONIC-ACID METABOLISM AND SHOCK SEQUELAE IN ENDOTOXEMIA

  • 1 January 1986
    • journal article
    • research article
    • Vol. 20  (2) , 151-159
Abstract
Previous studies have suggested that increased alpha adrenergic activity stimulated prostaglandin synthesis and may be involved in the modulation of eicosanoid metabolism. These observations prompted investigation of the effect of the alpha adrenergic receptor antagonist phenoxybenzamine and the cyclo-oxygenase inhibitor indomethacin on endotoxin-induced shock severity, and on plasma immunoreactive iTxB2 and i6-keto-PGF1a, the stable metabolites of TxA2 and PGI2, respectively. Pretreatment with indomethacin alone blunted the endotoxin- (8 mg/kg) induced hypoglycemia. Phenoxybenzamine pretreatment also blunted endotoxin-induced mortality (LD80), hypoglycemia, hemoconcentration, and decreased plasma beta-glucuronidase (BG). The combination of phenoxybenzamine and indomethacin resulted in the improvement of all indices of shock severity. Rats pretreated with phenoxybenzamine and indomethacin alone or conjointly also exhibited significantly (P < 0.05) enhanced survival compared to that of shocked control rats. Percent survival at 48 hr was 24, 64, 80, and 92 in untreated, indomethacin, phenoxybenzamine, and indomethacin + phenoxybenzamine treated, respectively. Mean plasma iTxB2 values at 30 min postendotoxin (15 mg/kg i.v.) were 1,532 .+-. 319 pg/ml (N = 10). Phenoxybenzamine pretreatment decreased iTxB2 to 719 .+-. 114 pg/ml (N = 10). Phenoxybenzamine pretreatment decreased iTxB2 to 719 .+-. 114 pg/ml (N = 10) (P < 0.05). Plasma i6-keto-PGF1a was increased 4 hr after endotoxin in shocked controls to 4,161 .+-. 885 pg/ml (N = 5) and attenuated by phenoxybenzamine to a value of 1,184 .+-. 363 pg/ml (N = 4) (P < 0.05). The results suggest that increased alpha adrenergic activity may be important stimulus for arachidonic acid metabolism during endotoxemia.