Prevention and suppression by azathioprine of venom-induced protein-losing gastropathy in dogs.

Irrigation of the dog's oxyntic glandular mucosa contained in a chronically prepared, vagally denervated, separated pouch of the dog's stomach with a solution (0.5 mg ml-1) of lyophilized venom of the hooded cobra (Naja naja) increases the permeability of the mucosa. If irrigation with venom solution is repeated at weekly intervals, the mucosa responds with increasing plasma-shedding which reaches a peak of 1-2 ml min-1 from roughly 60 cm2 of mucosa in 4-6 weeks. Plasma shedding in response to irrigation with venom gradually declines, leaving a permanent residual response of different magnitude in different dogs. Giving naive dogs the immunosuppressant azathioprine by mouth in a dose of 5 mg kg-1 day-1, beginning 1 week before the first irrigation with venom solution and continuing for 4 weeks, postpones the plasma-shedding response until the sixth or seventh week of venom irrigation. The plasma-shedding response is wholly or partially suppressed by further administration of azathioprine by mouth in a dose of 3.3 mg kg-1 day-1. These data support the hypothesis that the plasma-shedding response to repeated venom irrigation involves the immune system of the stomach.