Academic Journal
Pharmacological analysis of the inhibition produced by moxonidine and agmatine on the vasodepressor sensory CGRPergic outflow in pithed rats
| العنوان: | Pharmacological analysis of the inhibition produced by moxonidine and agmatine on the vasodepressor sensory CGRPergic outflow in pithed rats |
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| المؤلفون: | Rubio-Beltrán, Eloísa, Labastida-Ramírez, Alejandro, Hernández-Abreu, Oswaldo, MaassenVanDenBrink, Antoinette, Villalón, Carlos M |
| المصدر: | Rubio-Beltrán , E , Labastida-Ramírez , A , Hernández-Abreu , O , MaassenVanDenBrink , A & Villalón , C M 2017 , ' Pharmacological analysis of the inhibition produced by moxonidine and agmatine on the vasodepressor sensory CGRPergic outflow in pithed rats ' , European journal of pharmacology , vol. 812 , pp. 97-103 . https://doi.org/10.1016/j.ejphar.2017.07.020 |
| سنة النشر: | 2017 |
| المجموعة: | The University of Manchester: Research Explorer - Publications |
| مصطلحات موضوعية: | Agmatine/pharmacology, Animals, Calcitonin Gene-Related Peptide/metabolism, Dose-Response Relationship, Drug, Electric Stimulation, Hemodynamics/drug effects, Imidazoles/pharmacology, Male, Rats, Wistar, Sympathetic Nervous System/drug effects |
| الوصف: | Calcitonin gene-related peptide (CGRP) plays a role in several (patho)physiological functions, and modulation of its release is considered a therapeutic target. In this respect, electrical spinal (T 9 --T 12 ) stimulation of the perivascular sensory outflow in pithed rats produces vasodepressor responses mediated by CGRP release. This study investigated the role of imidazoline I 1 and I 2 receptors in the inhibition by moxonidine and agmatine of these vasodepressor responses. Male Wistar pithed rats (pretreated i.v. with 25mg/kg gallamine and 2mg/kg⋅min hexamethonium) received i.v. continuous infusions of methoxamine (20μg/kg⋅min) followed by physiological saline (0.02ml/min), moxonidine (1, 3, 10 or 30μg/kg⋅min) or agmatine (1000 or 3000μg/kg⋅min). Under these conditions, electrical stimulation (0.56-5.6Hz; 50V; 2ms) of the spinal cord (T9-T12) produced frequency-dependent vasodepressor responses which were: (i) unchanged during saline infusion; and (ii) inhibited during the above infusions of moxonidine or agmatine. Moreover, using i.v. administrations, the inhibition by 3μg/kg⋅min moxonidine or 3000μg/kg⋅min agmatine (which failed to inhibit the vasodepressor responses by α-CGRP; 0.1-1µg/kg) was: (i) unaltered after saline (1ml/kg), rauwolscine (300μg/kg; α2-adrenoceptor antagonist) or BU224 (300μg/kg; imidazoline I 2 receptor antagonist); and (ii) reversed after AGN 192403 (3000μg/kg; imidazoline I 1 receptor antagonist). This reversion was relatively more pronounced after AGN 192403 plus rauwolscine. These blocking doses of antagonists lacked any effects on the electrically-induced vasodepressor responses. Therefore, the inhibition of the vasodepressor sensory CGRPergic outflow by moxonidine and agmatine is mainly mediated by prejunctional imidazoline I 1 receptors on perivascular sensory nerves. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://research.manchester.ac.uk/en/publications/fbcde50e-a667-4c2a-b693-b80a5c381ccd |
| DOI: | 10.1016/j.ejphar.2017.07.020 |
| الاتاحة: | https://research.manchester.ac.uk/en/publications/fbcde50e-a667-4c2a-b693-b80a5c381ccd https://doi.org/10.1016/j.ejphar.2017.07.020 |
| Rights: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.14732983 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.ejphar.2017.07.020 |
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