[Changes in arachidonic acid-induced respiratory distress in streptozotocin-diabetic mice].
Using streptozotocin (STZ)-diabetic mice, we examined the respiratory distress induced by arachidonic acid. Male ddY mice were made diabetic by injecting STZ (170 mg/kg, i.p.) 2 weeks prior to the experiment. Control mice received the vehicle (citrate buffer, pH 4.6). The duration of respiratory distress was observed by a slow i.v.-injection of sodium arachidonic acid (AA) into the caudal vein of mice at the dose of 50 mg/kg. Aspirin was i.p.-administered 30 min before AA. OKY-046 (specific thromboxane A2 (TXA2) synthetase inhibitor), OP-41483 (stable prostacyclin analog) and 9, 11 epithia-11, 12-methano-TXA2 (STA2, stable TXA2 analog) were i.v.-administered 30 min before AA. The duration of respiratory distress induced by AA was significantly reduced in STZ-diabetic mice. Aspirin (10-50 mg/kg) and OKY-046 (25-100 mg/kg) enhanced the AA-induced respiratory distress in STZ-diabetic mice. OP-41483 (1-100 micrograms/kg) reduced the AA-induced effect in both control and STZ-diabetic mice. STA2 (10 micrograms/kg) enhanced the AA-induced effect in both control and STZ-diabetic mice. ONO-1078 (1-10 mg/kg) did not affect the AA-induced effect in both control and STZ-diabetic mice. TMK-688 (0.01-1 mg/kg) reduced the AA-induced effect in the control mice, but not in the STZ-diabetic mice. These results suggest an involvement of leukotriene in the respiratory response to AA in diabetic mice, especially when cyclooxygenase and TXA2 synthetase are inhibited.
Fujii
E
E
Department of Pharmacology, Tokyo Women's Medical College, Japan.
Nomoto
T
T
D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002867:Chromones / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003864:Depression, Chemical; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D051379:Mice; D012119:Respiration / Q000187:drug effects*; D013189:SRS-A / Q000037:antagonists & inhibitors; D013311:Streptozocin; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D002867:Chromones; D016861:Cyclooxygenase Inhibitors; D008689:Methacrylates; D013189:SRS-A; D016718:Arachidonic Acid; D013311:Streptozocin; D013930:Thromboxane-A Synthase; C034364:ozagrel; C047681:pranlukast