GABAergic mechanism in the rostral ventrolateral medulla contributes to the hypotension of moxonidine
| Autor: | Wen-Jun Yuan, Wang Yangkai, Ding-Feng Su, Wei-Zhong Wang, Jun-Feng Peng, Ming-Juan Xu, Wu Zhaotang, Xin Ni, Tao Sun, Wei Wang |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Sympathetic Nervous System Microinjections Physiology Microdialysis Blotting Western Blood Pressure GABAB receptor Kidney gamma-Aminobutyric acid Rats Sprague-Dawley GABA receptor Heart Rate Physiology (medical) Internal medicine medicine Animals GABA-A Receptor Antagonists Antihypertensive Agents gamma-Aminobutyric Acid Injections Intraventricular Medulla Oblongata Moxonidine Chemistry GABAA receptor Imidazoles Neural Inhibition Rostral ventrolateral medulla Bicuculline Receptors GABA-A Rats Infusions Intraventricular Endocrinology Receptors GABA-B nervous system Injections Intravenous GABAergic Hypotension Cardiology and Cardiovascular Medicine GABA-B Receptor Antagonists medicine.drug |
| Zdroj: | Cardiovascular Research. 89:473-481 |
| ISSN: | 1755-3245 0008-6363 |
| DOI: | 10.1093/cvr/cvq289 |
| Popis: | Aims The depressor action of the centrally antihypertensive drug moxonidine has been attributed to activation of I1-imidazoline receptor in the rostral ventrolateral medulla (RVLM). The objective of this study was to determine the role of the γ-aminobutyric acid (GABA) mechanisms in the RVLM in mediating the effect of moxonidine in anaesthetized normotensive rats. Methods and results The relationship between the effects of microinjection or picoinjection of moxonidine and the functional state of GABA receptors at the level of the RVLM or pre-sympathetic neuron was determined. Microdialysis was performed to detect the effect of moxonidine on the release of GABA in the RVLM. Western blot analysis was carried out to test the effect of chronic intracerebroventricular injection of moxonidine on the protein expression of GABA receptors in the RVLM. Pre-treatment with the GABAA or GABAB receptor antagonist bicuculline (5 pmol) or CGP35348 (200 pmol), respectively, microinjected into the RVLM significantly attenuated the decrease in blood pressure and renal sympathetic nerve activity induced by moxonidine. In 22 moxonidine-sensitive pre-sympathetic neurons in the RVLM, picoinjection of bicuculline (100 fmol/5 nL) significantly attenuated the neuronal inhibition evoked by moxonidine (100 pmol/5 nL). The release of GABA in the RVLM was increased after intravenous moxonidine (50 μg/kg). Central infusion of moxonidine upregulated the protein expression of both GABAA and GABAB receptors in the RVLM. Conclusion The current data demonstrate that GABAergic mechanisms in the RVLM are responsible for the hypotension and sympathoinhibition of moxonidine. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|