{'fraction_non_alphanumeric': 0.05558288243974422, 'fraction_numerical': 0.03984259714707329, 'mean_word_length': 5.2392638036809815, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Concentration-dependent, stereoselective inhibition of the endotoxin-induced hemoconcentration in conscious rats with the peptidoleukotriene receptor antagonist SK & F 104353.

Endotoxemia is associated with increases in a number of humoral mediators including vasopressin, thromboxane and leukotrienes (LT), all of which may participate in the pathophysiologic responses to endotoxemia. Previous studies from our laboratory demonstrated that endotoxin-induced hemoconcentration was attenuated with a peptidoleukotriene receptor antagonist, SK & F 104353. The purpose of this study was to investigate further the mechanism of endotoxin-induced hemoconcentration. Injection of LTD4 (51 nmol/kg, i.v.) produced an increase in the hematocrit of conscious male Sprague-Dawley rats: administration of SK & F 104353 (2 mg/kg, i.v. + 10 mg/kg/h, i.v. infusion) blocked completely this response to exogenous LTD4. Injection of Salmonella enteritidis endotoxin (30 mg/kg, i.v.) increased the hematocrit from 41 +/- 1 vol% to 55 +/- 1 vol%. Following pretreatment with SK & F 104353 (2 mg/kg, i.v. + 10 mg/kg/h, i.v.), the hemoconcentration was attenuated to 46 +/- 1 vol% (p less than 0.01). Simultaneous determination of plasma drug concentrations over a range of doses indicated that inhibition of the hemoconcentration produced by SK & F 104353 was concentration-dependent (IC30 = 0.5 microgram/ml). The IC30 for the stereoisomer, SK & F 104373, was 50 micrograms/ml. The 5-lipoxygenase/cyclooxygenase inhibitors, SK & F 86002 and BW 775C, also attenuated the endotoxin-induced increase in hematocrit, whereas indomethacin, heparin, daltroban, or the selective V1 vasopressin receptor antagonist [d(CH2)5Tyr(Me)]AVP did not significantly affect the endotoxin-induced hemoconcentration. The endotoxin-induced hemoconcentration was inhibited in a concentration-dependent, stereoselective manner with a peptidoleukotriene receptor antagonist, and by 5-lipoxygenase inhibitors, indicating that this response is mediated by peptidoleukotrienes.