Hypothalamic release of nitric oxide and interaction with amino acid neurotransmitters in chronically uraemic rats
| Autor: | Johannes Woitzik, Marcel Vogel, Meike Hömme, Markus Daschner, Franz Schaefer, Nils Abromeit |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Microdialysis N-Methylaspartate Hypothalamus Gonadotropin-releasing hormone S-Nitroso-N-Acetylpenicillamine Neurotransmission Biology Nitric Oxide Nephrectomy Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Internal medicine medicine Animals Castration RNA Messenger Enzyme Inhibitors Neurotransmitter Uremia Neurons chemistry.chemical_classification Neurotransmitter Agents Transplantation Rats Amino acid Nitric oxide synthase Endocrinology 2-Amino-5-phosphonovalerate chemistry Nephrology biology.protein Nitric Oxide Synthase |
| Zdroj: | Nephrology Dialysis Transplantation. 20:1566-1572 |
| ISSN: | 1460-2385 0931-0509 |
| DOI: | 10.1093/ndt/gfh878 |
| Popis: | Background. The activity of the hypothalamic gonadotrophin-releasing hormone (GnRH) pulse generator is diminished in uraemia. Since GnRH release is influenced by nitric oxide (NO) neurotransmission, we examined the integrity of hypothalamic NO neurotransmission in the chronically uraemic rat model. Methods. Adult male castrated rats were rendered uraemic by two-stage 5/6 nephrectomy. Basal, N-methyl-D-aspartate (NMDA)-stimulated and DL-2amino-5-phosphonovaleric acid (AP-5)-inhibited NO outflow was measured in uraemic and shamnephrectomized control animals via a microdialysis probe in the medial preoptic area (MPOA). The influence of the noradrenergic system was evaluated by blocking noradrenergic neurons with N-(2chloroethyl)-N-ethyl 2-bromobenzylamine (DSP-4). The activity of different NO synthase (NOS) isoforms was investigated by administration of the isoformspecific NOS inhibitors S-methyl-L-thiocitrulline (SMLT) and L-N 6 -(1-iminoethyl)-lysine (L-NIL). Moreover, hypothalamic mRNA expression of the individual NOS isoforms was quantitated by real-time reverse transcriptase–polymerase chain reaction. Effects of NO on amino acid outflow were assessed by addition of the NO donor S-nitroso-Nacetyl-penicillamine (SNAP). Results. The expression of different NOS species and basal NO outflow did not differ between uraemic and control animals. Administration of the NO donor SNAP increased local NO production and amino acid outflow similarly in both groups. SMLT but not L-NIL, an inhibitor of the inducible NOS isoform, reduced NO outflow in both groups. AP-5 equally decreased, and noradrenergic blockade increased NMDA-stimulated NO outflow in both groups. Conclusions. NO is produced locally and may interfere with amino acid neurotransmission in the rat MPOA. Uraemia did not interfere with NO neurotransmission in our study. |
| Databáze: | OpenAIRE |
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