NO inhibition of the magnocellular neuroendocrine system in rats is independent of cGMP signaling pathway

• Published in: Experimental neurology Vol. 184; no. 2; pp. 846 - 856
• Main Authors: Lee Terrell, Mary, Salas, Nilson, Bui, V, Summy-Long, J.Y, Kadekaro, M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.12.2003; Elsevier
• Subjects: [ 14C]citrulline; Animals; Biological and medical sciences; Citrulline - metabolism; Consciousness; Cyclic GMP - administration & dosage; Cyclic GMP - analogs & derivatives; Cyclic GMP - pharmacology; Cyclic GMP - physiology; Dehydration; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacology; Guanylate Cyclase - metabolism; Hypothalamo-Hypophyseal System - physiology; Injections, Intraventricular; Isotonic Solutions - administration & dosage; Male; Medical sciences; Microdialysis; Neurology; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; NOS; Oxytocin; Oxytocin - analysis; Oxytocin - drug effects; Pituitary Gland, Posterior - enzymology; Rats; Rats, Sprague-Dawley; Saline Solution, Hypertonic - administration & dosage; Signal Transduction - physiology; Sodium Chloride; Soluble guanylyl cyclase; Supraoptic nucleus; Supraoptic Nucleus - drug effects; Supraoptic Nucleus - physiology; Vasopressin; Vasopressins - analysis; Vasopressins - drug effects; Water-Electrolyte Balance - physiology; Microdialysis; NOS; Oxytocin; Soluble guanylyl cyclase; [ 14C]citrulline; Vasopressin; Supraoptic nucleus; Intravenous administration; Rat; Central nervous system; Phosphorus-oxygen lyases; Insertion; Lyases; Hypothalamus; Cerebrospinal fluid; Synthase; Guanylate cyclase; Neuropeptide; Recovery; Encephalon; Signal transduction; [14C]citrulline; Arginine; Modulation; Neurohypophyseal hormone; Inhibition; Hypertonic solution; Nervous system diseases; Enzyme; Rodentia; 3',5'-GMP; Vertebrata; Pituitary hormone; Mammalia; Animal; Nitric oxide; Dimethyl sulfoxide
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/S0014-4886(03)00305-4

Our objective was to test the hypothesis that the cGMP signal-transduction mechanism mediates nitric oxide's (NO) modulation of oxytocin (OT) and vasopressin (VP) secretion from the hypothalamo-neurohypophysial system. Three studies were conducted in adult male Sprague–Dawley rats: (1a) Euhydrated rats received an intracerebroventricular (icv) infusion (1 μl/min for 30 min) of artificial cerebrospinal fluid (aCSF), vehicle (2.6% dimethyl sulfoxide [DMSO]) or 1 H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (0.05 μg/μl), an inhibitor of soluble guanylyl cyclase (sGC). ODQ did not affect basal levels of plasma VP or OT; (1b) Rats dehydrated for 24 h received aCSF or 8-Br-cGMP (icv), a membrane-permeable analog of cGMP, and plasma hormones were measured 2 min later. 8-Br-cGMP did not significantly change VP or OT levels; (2) Rats ingested water or 2% NaCl for 4 days, and NO synthase (NOS) and sGC activities were measured in posterior pituitaries, the anatomical site of hormone secretion. Salt loading enhanced ( P < 0.001) production of [ 14C]citrulline, the coproduct of NO synthesis, without altering cGMP; (3) One SON was microdialyzed with [ 14C]arginine and NOS and sGC activities were quantified in microdialysates during intravenous (iv) infusion of isotonic or hypertonic saline in awake and anesthetized rats. In awake rats, [ 14C]citrulline recovery, but not cGMP, increased ( P < 0.05) during intravenous infusion of both isotonic and hypertonic solutions, and after insertion of microdialysis probe itself. In anesthetized rats, however, where basal NOS activity is low, intravenous infusion of hypertonic, but not isotonic solution, increased [ 14C]citrulline recovery without affecting cGMP. Thus, in the forebrain, neither NO produced basally nor during osmotic stimulation depends on cGMP to modulate plasma vasopressin and oxytocin secretion.