Nitric oxide and the oxytocin system in pregnancy.
We examined the functional role of the nitric oxide (NO)-producing system in magnocellular neurons and how this changes at the end of pregnancy, using a combination of blood sampling and oxytocin radioimmunoassay, electrophysiology, immunocytochemistry for Fos expression, and in situ hybridization histochemistry. In urethane-anesthetized virgin rats, systemic administration of NO synthase (NOS) inhibitors led to a facilitation of oxytocin release evoked by hyperosmotic stimulation. Direct application of the NO donor sodium nitroprusside to the supraoptic nucleus by in vivo microdialysis inhibited the electrical activity of both oxytocin neurons and vasopressin neurons, whereas direct application of an NOS inhibitor increased electrical activity, indicating that endogenous NO acts within the supraoptic nucleus to inhibit neuronal activity. However, during late pregnancy, the influence of endogenous NO is dramatically downregulated, reflected by a reduced expression of neuronal NOS mRNA in these neurons and a loss of efficacy of NOS inhibitors on stimulus-evoked oxytocin release. This downregulation may cause the oxytocin system to become more excitable at term, resulting in the capacity for greater release of oxytocin during parturition.
Srisawat
R
R
Department of Biomedical Sciences, University of Edinburgh Medical School, Edinburgh EH8 9XD, United Kingdom.
Ludwig
M
M
Bull
P M
PM
Douglas
A J
AJ
Russell
J A
JA
Leng
G
G
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D017551:Microdialysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010121:Oxytocin / Q000097:blood / Q000502:physiology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000502:physiology*; D014667:Vasopressins / Q000502:physiology
D014667:Vasopressins; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D010121:Oxytocin; D019331:NG-Nitroarginine Methyl Ester