Vasorelaxant effects of the chronic treatment with melatonin on mesenteric artery and aorta of spontaneously hypertensive rats

Vasorelaxant effects of the chronic treatment with melatonin on mesenteric artery and aorta of spontaneously hypertensive rats
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DOI:
10.1097/00004872-200108000-00004
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发表时间:
2001-08-01
影响因子:
4.9
通讯作者:
de Champlain, J
de Champlain, J
中科院分区:
医学2区
文献类型:
--
作者:
Girouard, H;Chulak, C;de Champlain, J

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目的探讨慢性褪黑素治疗对自发性高血压大鼠(SHR)和Wistar-Kyoto (WKY)大鼠动脉压的影响及对血管毒毒碱和NO合成酶(NOS)通路的改善作用。设计与方法在4周的时间里,对每天服用30mg /kg褪黑素的清醒大鼠进行平均动脉压(MAP)、收缩压(SBP)、舒张压(DBP)和心率(HR)评估。静脉注射NOS抑制剂N(omega)-硝基- l -精氨酸甲酯(L-NAME)后,评估MAP的变化。研究了乙酰胆碱(Ach)、硝普钠(SNP)和钙离子载体A23187在褪黑素治疗或不治疗时对肠系膜床和主动脉环的松弛作用。结果褪黑素显著降低SHR患者的MAP、SBP、DBP和HR (P < 0.05)。L-NAME对褪黑激素处理的SHR的MAP升高幅度与WKY组相同,且显著高于未处理SHR组(P < 0.05)。褪黑素治疗使SHR大鼠肠系膜动脉对A23187的最大舒张程度提高到WKY水平(P < 0.001),使SHR大鼠和WKY大鼠的Ach和A23187诱导的主动脉血管舒张程度略有增加(P < 0.05)。结论褪黑素在SHR患者中具有心动过缓和降压作用。褪黑素增强SHR和WKY大鼠肠系动脉和主动脉内皮依赖性血管舒张(Ach和/或A23187),褪黑素治疗的SHR在L-NAME治疗后MAP升高,提示褪黑素改善血管NOS通路活性的作用。(C) 2001 Lippincott Williams & Wilkins。
Objective To investigate the effect of a chronic treatment with melatonin on arterial pressure and a possible improvement of the vascular muscarinic and NO synthase (NOS) pathways in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats.Design and methods Mean arterial pressure (MAP), systolic (SBP), diastolic blood pressure (DBP), and heart rate (HR) were evaluated in conscious rats treated with 30 mg/kg per day of melatonin during 4 weeks. Changes in MAP were evaluated following an intravenous injection of the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). Relaxant effects of acetylcholine (Ach), sodium nitroprusside (SNP), and the calcium ionophore A23187 were examined on mesenteric beds and aortic rings with or without treatment with melatonin.Results Melatonin produced a significant reduction of MAP, SBP, DBP and HR in SHR (P < 0.05). L-NAME increased the MAP of melatonin-treated SHR by the same magnitude as that of WKY rats which was significantly higher than that of non-treated SHR (P < 0.05). Melatonin treatment improved the maximal relaxation of mesenteric arteries to A23187 in SHR (P < 0.001) to the WKY level and caused a slight increament in Ach- and A23187-induced vasodilations in aorta from SHR and WKY rats (P < 0.05).Conclusion The present study showed that melatonin exerted a bradycardic and an antihypertensive action in SHR. The enhancement by melatonin of the endothelium-dependent vasodilation (Ach and/or A23187) in mesenteric artery and aorta from SHR and WKY rats and the higher increase in MAP following L-NAME treatment in melatonin-treated SHR suggest the contribution of an improved vascular NOS pathway activity in the hypotensive effect of melatonin. (C) 2001 Lippincott Williams & Wilkins.