Girouard H, Chulak C, Lejossec M, Lamontagne D, de Champlain J
Department of Physiology, Faculty of Medicine, University of Montréal, Succursale Centreville, Québec, Canada.
J Hypertens. 2001 Aug;19(8):1369-77. doi: 10.1097/00004872-200108000-00004.
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.
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.
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 increment in Ach- and A23187-induced vasodilations in aorta from SHR and WKY rats (P < 0.05).
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.
研究褪黑素长期治疗对自发性高血压大鼠（SHR）和Wistar-Kyoto（WKY）大鼠动脉血压的影响以及对血管毒蕈碱和一氧化氮合酶（NOS）途径的可能改善作用。
对清醒大鼠进行为期4周、每天30mg/kg褪黑素的治疗，评估其平均动脉压（MAP）、收缩压（SBP）、舒张压（DBP）和心率（HR）。静脉注射NOS抑制剂N-ω-硝基-L-精氨酸甲酯（L-NAME）后评估MAP的变化。检测乙酰胆碱（Ach）、硝普钠（SNP）和钙离子载体A23187对经或未经褪黑素治疗的肠系膜床和主动脉环的舒张作用。
褪黑素使SHR的MAP、SBP、DBP和HR显著降低（P<0.05）。L-NAME使褪黑素治疗的SHR的MAP升高幅度与WKY大鼠相同，且显著高于未治疗的SHR（P<0.05）。褪黑素治疗使SHR肠系膜动脉对A23187的最大舒张改善至WKY水平（P<0.001），并使SHR和WKY大鼠主动脉中Ach和A23187诱导的血管舒张略有增加（P<0.05）。
本研究表明褪黑素对SHR具有减慢心率和降压作用。褪黑素增强SHR和WKY大鼠肠系膜动脉和主动脉中内皮依赖性血管舒张（Ach和/或A23187），以及褪黑素治疗的SHR经L-NAME治疗后MAP升高幅度更大，提示血管NOS途径活性改善在褪黑素降压作用中发挥了作用。
