title: Electrophysiological and immunocytochemical evidence for a cGMP-mediated inhibition of subfornical organ neurons by nitric oxide.
abstract: The activation of neurons in the subfornical organ (SFO) by angiotensin II (AngII) is well established and is widely regarded as the basis for the AngII-induced increase in water intake. Application of the nitric oxide (NO) donor sodium nitroprusside (SNP) led to an inhibition of the spontaneous electrical activity in 96% of the neurons sensitive for SNP (n = 50). In addition, the firing rate in 60% of the neurons inhibited by SNP decreased in response to superfusion with the natural substrate of the NO synthase (NOS) L-arginine whereas 70% increased their frequency after application of the NOS blocker NG-monomethyl-L-arginine (L-NMMA; n = 10). The inhibitory effect of SNP could be mimicked by application of membrane-permeable 8-Br-cGMP. The presence of nNOS, the neuronal isoform of NOS, was demonstrated immunocytochemically and using the NADPH-diaphorase technique on SFO slices. Using a highly selective antibody against cGMP in formaldehyde-fixed tissue, the NO donors SNP, 3-morpholinosydnonimine (SIN-1), and S-nitroso-N-acetyl-DL-penicillamine (SNAP) caused a strong increase in cGMP formation when applied under the same conditions as used for the electrophysiological recordings. These electrophysiological results suggest an important role for NO in SFO-mediated responses and offer a plausible explanation for the in vivo-observed opposite effects of AngII and NO on water intake.
authors.affiliation: Max-Planck-Institut für Physiologische und Klinische Forschung, W. G. Kerckhoff-Institut, 61231 Bad Nauheim, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Rauch
authors.forename: H A
authors.initials: HA
authors.lastname: Schmid
authors.forename: J
authors.initials: J
authors.lastname: deVente
authors.forename: E
authors.initials: E
authors.lastname: Simon
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004594:Electrophysiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D013356:Subfornical Organ / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
chemical_list: D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D009252:NADPH Dehydrogenase; D006152:Cyclic GMP