Prostacyclin and noradrenaline in peripheral nerve of chronic experimental diabetes in rats

Noradrenaline levels in the superior cervical ganglion and sciatic nerve were significantly reduced in chronic streptozotocin-induced diabetes in rats. Sciatic nerve sheath in vitro biosynthesis of 6-keto prostaglandin F1 alpha (6KPGF1 alpha; the stable metabolite of prostacyclin) was significantly reduced but not in acute experimental diabetes. Nerves with reduced 6KPGF1 alpha had an excessive response to arachidonic acid stimulation. We suggest that the reduced endogenous biosynthesis of prostacyclin is due to reduced substrate availability, possibly due to the reduced noradrenaline. The implications of these findings on the pathogenesis of diabetic neuropathy are discussed. Neuropathy was found to involve all fibre populations studied (motor, sensory and sympathetic) and progressed with duration of diabetes.