Further studies on the hypoxia produced by canatoxin in rats

Canatoxin, a convulsant neurotoxin from the seeds of Canavalia ensiformis, induces lipoxygenase-dependent hypoxia in rats which is blocked by hexamethonium. The purpose of the present study was to examine the relationship between canatoxin-induced hypoxia and bronchoconstriction. Since several effects of the toxin are very similar to those described for morphine and opioid-like peptides, the effects of opioid antagonists were also investigated. Pretreatment of male, adult Wistar rats (200-250 g) with cyproheptadine (80 micrograms/kg, ip, N = 6) and isoproterenol (100 micrograms/kg, ip, N = 6) partially blocked (% variation of pO2: CNTX alone: -26.67 +/- 2.56, N = 6; with cyproheptadine: -16.15 +/- 2.97*, N = 6; with isoproterenol: -17.73 +/- 1.93*, N = 6; *P < 0.05 as compared to CNTX alone) the hypoxia but no effect was observed with diphenhydramine (2 mg/kg, ip, N = 6) or atropine (2 mg/kg, ip, N = 6). The hypoxemic effect of canatoxin (100 micrograms/kg, i.v., 20 min, N = 6) was also almost completely blocked with either naloxone (1 mg/kg, sc, N = 6) or naltrexone (5 mg/kg, sc, N = 6). The results presented here provide evidence suggesting that both opioid peptides and bronchoconstriction seem to play a role in the hypoxia caused by canatoxin.