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首页> 外文期刊>Life sciences >Effect of some acute and prophylactic antimigraine drugs on the vasodepressor sensory CGRPergic outflow in pithed rats.
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Effect of some acute and prophylactic antimigraine drugs on the vasodepressor sensory CGRPergic outflow in pithed rats.

机译：某些急性和预防性偏头痛药物对有髓大鼠的降压药感觉CGRPergic流出的影响。

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AIMS: This study analyzed in pithed rats the effect of several acute and prophylactic antimigraine drugs on the CGRPergic vasodepressor sensory outflow, in an attempt to investigate systemic cardiovascular effects in a model unrelated to migraine. MAIN METHODS: Male Wistar pithed rats were pretreated with continuous i.v. infusions of hexamethonium (2 microg/kg.min; to block autonomic outflow) and methoxamine (15-20 microg/kg.min; to maintain diastolic blood pressure at around 130 mmHg). Under these conditions, the effect of both electrical stimulation (0.56-5.6 Hz; 50 V and 2 ms) of the spinal cord (T(9)-T(12)) or i.v. bolus injections of exogenous alpha-CGRP (0.1-1 microg/kg) were studied in animals pretreated with continuous i.v. infusions of sumatriptan (1-100 microg/kg.min), ergotamine (0.18-0.56 microg/kg.min), dihydroergotamine (1-10 microg/kg.min), magnesium valproate (1000-1800 microg/kg.min), propranolol (100-300 microg/kg.min) or their respective vehicles. KEY FINDINGS: Electrical stimulationof the spinal cord and i.v. bolus injections of exogenous alpha-CGRP resulted in, respectively, frequency- and dose-dependent decreases in diastolic blood pressure without affecting heart rate. Moreover, the infusions of sumatriptan, ergotamine and dihydroergotamine, but not of magnesium valproate, propranolol or their respective vehicles, dose-dependently inhibited the vasodepressor responses to electrical stimulation. In contrast, sumatriptan (10 microg/kg.min), ergotamine (0.31 microg/kg.min) and dihydroergotamine (3 microg/kg.min) failed to inhibit the vasodepressor responses to exogenous alpha-CGRP. SIGNIFICANCE: The above findings suggest that the acute (rather than the prophylactic) antimigraine drugs attenuate the vasodepressor sensory outflow mainly by prejunctional mechanisms. This may be of particular relevance when considering potential cardiovascular adverse effects by acute antimigraine drugs.
机译：目的：本研究在成年大鼠中分析了几种急性和预防性偏头痛药物对CGRPergic血管加压素感觉流出的影响，试图研究与偏头痛无关的系统性心血管作用。主要方法：雄性Wistar髓系大鼠经连续静脉内预处理。输注六甲铵（2 microg / kg.min;阻止自主流出）和甲氧胺（15-20 microg / kg.min;使舒张压保持在130 mmHg左右）。在这些条件下，脊髓（T（9）-T（12））或静脉电刺激（0.56-5.6 Hz; 50 V和2 ms）都受到影响。在连续静脉内预处理的动物中研究了外源性α-CGRP（0.1-1微克/千克）的大剂量注射。舒马曲坦（1-100微克/千克。分钟），麦角胺（0.18-0.56微克/千克。分钟），二氢麦角胺（1-10微克/千克。分钟），丙戊酸镁（1000-1800微克/千克。分钟） ，普萘洛尔（100-300 microg / kg.min）或它们各自的媒介物。主要发现：脊髓和静脉电刺激大剂量注射外源性α-CGRP分别导致舒张压的频率和剂量依赖性降低，而不会影响心率。而且，输注舒马曲坦，麦角胺和二氢麦角胺，但不注射丙戊酸镁，普萘洛尔或它们各自的溶媒，剂量依赖性地抑制了血管舒缩剂对电刺激的反应。相反，舒马曲坦（10 microg / kg.min），麦角胺（0.31 microg / kg.min）和二氢麦角胺（3 microg / kg.min）无法抑制对外源性α-CGRP的血管舒缩压反应。意义：以上发现表明，急性（而非预防性）抗偏头痛药物主要通过结节机制减轻了血管舒缩剂的感觉流出。当考虑急性抗偏头痛药物可能引起的心血管不良反应时，这可能特别相关。

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