α2A-adrenoceptors, but not nitric oxide, mediate the peripheral cardiac sympatho-inhibition of moxonidine
| Autor: | Yesenia Silva-Belmares, María Antonia González-Zavala, Luis E. Cobos-Puc, David Centurión, Hilda Aguayo-Morales |
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| Rok vydání: | 2016 |
| Předmět: |
Male
medicine.medical_specialty Sympathetic nervous system Sympathetic Nervous System Stellate Ganglion Nitric Oxide Synthase Type II Imiloxan Nitric Oxide Synthase Type I 030204 cardiovascular system & hematology Pharmacology Gene Expression Regulation Enzymologic Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Receptors Adrenergic alpha-2 Internal medicine Tachycardia medicine Animals Rats Wistar Moxonidine biology Chemistry BRL-44408 Antagonist Hemodynamics Imidazoles Heart Adrenergic alpha-2 Receptor Antagonists Rats Nitric oxide synthase Endocrinology medicine.anatomical_structure NG-Nitroarginine Methyl Ester Stellate ganglion biology.protein 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | European journal of pharmacology. 782 |
| ISSN: | 1879-0712 |
| Popis: | Moxonidine centrally inhibits the sympathetic activity through the I1-imidazoline receptor and nitric oxide. In addition, inhibits the peripheral cardiac sympathetic outflow by α2-adrenoceptors/I1-imidazoline receptors, although the role of α2-adrenoceptor subtypes or nitric oxide in the cardiac sympatho-inhibition induced by moxonidine are unknown. Therefore, the cardiac sympatho-inhibition induced by moxonidine (10μg/kgmin) was evaluated before and after of the treatment with the following antagonists/inhibitor: (1) BRL 44408, (300μg/kg, α2A), imiloxan, (3000μg/kg, α2B), and JP-1302, (300μg/kg, α2C), in animals pretreated with AGN 192403 (3000μg/kg, I1 antagonist); (2) N(ω)-nitro-l-arginine methyl ester (l-NAME; 34, 100, and 340μg/kgmin); and (3) the combinations of the highest dose of l-NAME plus AGN 192403 or BRL 44408. Additionally, the expression of the neuronal (nNOS) and inducible (iNOS) nitric oxide synthase in the stellate ganglion was determined after treatment with moxonidine (i.p. 0.56mg/kg daily, during one week). The cardiac sympatho-inhibition of 10μg/kgmin moxonidine was: (1) unaffected by imiloxan and JP-1302, under pretreatment with AGN 192403, or l-NAME (34, 100 and 340μg/kgmin) given alone; (2) partially antagonized by the combination of 340 μg/kgmin l-NAME plus BRL 44408; and (3) abolished by BRL 44408 under treatment with AGN 192403. Furthermore, moxonidine did not modify the nNOS or iNOS protein expression in the stellate ganglion, the main source of postganglionic sympathetic neurons innervating the heart. In conclusion, our results suggest that the peripheral cardiac sympatho-inhibition induced by moxonidine is mediated by α2A-adrenoceptor subtype but not by nitric oxide. |
| Databáze: | OpenAIRE |
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