Chronic Sarpogrelate Treatment Reveals 5-HT7 Receptor in the Serotonergic Inhibition of the Rat Vagal Bradycardia
| Autor: | José Ángel García-Pedraza, Asunción Morán, Monica Garcia, María Luisa Martín, Nélida Eleno |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Bradycardia Vagus Nerve Stimulation Receptor expression medicine.medical_treatment Sarpogrelate 030204 cardiovascular system & hematology Pharmacology Serotonergic Drug Administration Schedule 5-HT7 receptor 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Heart Rate Animals Medicine Rats Wistar Dose-Response Relationship Drug business.industry Succinates Vagus Nerve Rats Vagus nerve Treatment Outcome chemistry Receptors Serotonin Serotonin Antagonists medicine.symptom Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery Vagus nerve stimulation Acetylcholine medicine.drug |
| Zdroj: | Journal of Cardiovascular Pharmacology. 69:13-22 |
| ISSN: | 0160-2446 |
| Popis: | 5-Hydroxytryptamine (5-HT) modulates the cardiac parasympathetic neurotransmission, inhibiting the bradyarrhythmia by 5-HT2 receptor activation. We aimed to determine whether the chronic selective 5-HT2 blockade (sarpogrelate) could modify the serotonergic modulation on vagal cardiac outflow in pithed rat. Bradycardic responses in rats treated with sarpogrelate (30 mg·kg·d; orally) were obtained by electrical stimulation of the vagal fibers (3, 6, and 9 Hz) or intravenous (IV) injections of acetylcholine (1, 5, and 10 μg/kg). 5-HT7 receptor expression was quantified by Western blot in vagus nerve and right atrium. The IV administration of 5-HT (10-200 μg/kg) dose dependently decreased the vagally induced bradycardia, and agonists 5-CT (5-HT1/7), 8-OH-DPAT (5-HT1A), or AS-19 (5-HT7) (50 μg/kg each) mimicked the 5-HT-induced inhibitory effect. Neither agonists CGS-12066B (5-HT1B), L-694,247 (5-HT1D), nor 1-phenylbiguanide (5-HT3) modified the electrically-induced bradycardic responses. Moreover, SB-258719 (5-HT7 antagonist) abolished the 5-HT-, 5-CT-, 8-OH-DPAT-, and AS-19-induced bradycardia inhibition; 5-HT or AS-19 did not modify the bradycardia induced by IV acetylcholine; and 5-HT7 receptor was expressed in both the vagus nerve and the right atrium. Our outcomes suggest that blocking chronically 5-HT2 receptors modifies the serotonergic influence on cardiac vagal neurotransmission exhibiting 5-HT as an exclusively inhibitory agent via prejunctional 5-HT7 receptor. |
| Databáze: | OpenAIRE |
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