Nitric oxide and the oxytocin system in pregnancy

We examined the functional role of the nitric oxide (NO) producing system i n magnocellular neurons and how this changes at the end of pregnancy, using a combination of blood sampling and oxytocin radioimmunoassay, electrophys iology, immunocytochemistry for Fos expression, and in situ hybridization h istochemistry. In urethane-anesthetized virgin rats, systemic administratio n of NO synthase (NOS) inhibitors led to a facilitation of oxytocin release evoked by hyperosmotic stimulation. Direct application of the NO donor sod ium nitroprusside to the supraoptic nucleus by in vivo microdialysis inhibi ted the electrical activity of both oxytocin neurons and vasopressin neuron s, whereas direct application of an NOS inhibitor increased electrical acti vity, indicating that endogenous NO acts within the supraoptic nucleus to i nhibit neuronal activity. However, during late pregnancy, the influence of endogenous NO is dramatically downregulated, reflected by a reduced express ion of neuronal NOS mRNA in these neurons and a loss of efficacy of NOS inh ibitors on stimulus-evoked oxytocin release. This downregulation may cause the oxytocin system to become more excitable at term, resulting in the capa city for greater release of oxytocin during parturition.