The field-stimulated vas deferens of the streptozotocin-diabetic mouse: effects of prazosin, alpha, beta-methylene ATP, and variation of stimulation parameters

Abstract

The question of diabetic neuropathy was studied in the field-stimulated isolated vas deferens of the mouse. The animals were treated with either buffer or streptozotocin (170 mg/kg i.v.) 2 or 4 weeks, respectively, beforehand. Stimulus-response relationships were tested by variation of frequency (VF) at constant pulse width and by variation of pulse width (VP) at constant frequency. The adrenergic twitch component was eliminated by prazosin (1 microM) and the purinergic component by alpha, beta-methylene ATP (MeATP, 10 microM). The diabetes did not alter the muscular contractility (tested with KCl) and left the twitch-inhibiting effects of prazosin and MeATP unchanged, thereby revealing no difference in susceptibility between noradrenergic and purinergic mechanisms. However, in diabetic vasa, the maximal effectiveness of stimulation was decreased with VF but not VP, whereas the sensitivity of intramural neurons (50% effective frequency or pulse width, respectively) was unchanged with VF and reduced with VP. This may suggest that the diabetic neuron release less transmitter (VF), which can be compensated for by the activation of less sensitive neurons (VP). Actually, the uptake of 3H-noradrenaline into the (4 weeks-) diabetic vas was normal but the stimulation-induced fractional release of tritium was decreased by 26%. It is concluded that a sympathetic neuropathy occurred in the vas deferens of the streptozotocin-diabetic mouse.