Simko Fedor, Pechanova Olga, Pelouch Vaclav, Krajcirovicova Kristina, Mullerova Martina, Bednarova Kristina, Adamcova Michaela, Paulis Ludovit
Department of Pathophysiology, School Medicine, Comenius University, Bratislava, Slovak Republic.
J Hypertens Suppl. 2009 Aug;27(6):S5-10. doi: 10.1097/01.hjh.0000358830.95439.e8.
Melatonin was shown to reduce blood pressure, oxidative load and to increase nitric oxide bioavailability predisposing melatonin to have antiremodelling potential.
The aim of this study was to show whether melatonin can reverse left ventricular remodelling in spontaneously hypertensive rats (SHR) and to compare this potential protective effect with captopril, spironolactone, or simvastatin.
Six groups of 3-month old rats (eight per group) were treated for 5 weeks: control untreated Wistar rats, control SHR, SHR plus melatonin (10 mg/kg per 24 h), SHR plus captopril (100 mg/kg per 24 h), SHR plus spironolactone (200 mg/kg per 24 h) and SHR plus simvastatin (10 mg/kg per 24 h). Their systolic blood pressure (SBP) was measured by the tail-cuff method. The relative weights of the left ventricle, nitric oxide synthase (NOS) activity, endothelial NOS and nuclear factor kappa B (NF-kappaB) protein expression, conjugated dienes concentration, level of collagenous proteins and hydroxyproline were measured.
SBP was reduced by all drugs investigated but most prominently by captopril in SHR. The activity of NOS and endothelial NOS expression increased in the left ventricles of SHR compared with controls. Melatonin and spironolactone further increased NOS expression. Left ventricular oxidative load, estimated by NF-kappaB expression and conjugated dienes concentration, increased in SHR. Only melatonin reduced NF-kappaB expression and decreased conjugated diens concentration. Only captopril reduced left ventricular hypertrophy in SHR, whereas melatonin reduced collagenous protein concentration and hydroxyproline content in the left ventricle.
It is concluded that although melatonin, in comparison with captopril, did not reverse left ventricle hypertrophy, it reversed left ventricular fibrosis. This protection by melatonin may be caused by its prominent antioxidative effect.
褪黑素可降低血压、减轻氧化负荷并提高一氧化氮生物利用度，使其具有抗重塑潜力。
本研究旨在探讨褪黑素能否逆转自发性高血压大鼠（SHR）的左心室重塑，并将这种潜在的保护作用与卡托普利、螺内酯或辛伐他汀进行比较。
将六组3月龄大鼠（每组8只）进行为期5周的治疗：未治疗的对照Wistar大鼠、对照SHR、SHR加褪黑素（每24小时10毫克/千克）、SHR加卡托普利（每24小时100毫克/千克）、SHR加螺内酯（每24小时200毫克/千克）和SHR加辛伐他汀（每24小时10毫克/千克）。采用尾套法测量其收缩压（SBP）。测量左心室相对重量、一氧化氮合酶（NOS）活性、内皮型NOS和核因子κB（NF-κB）蛋白表达、共轭二烯浓度、胶原蛋白水平和羟脯氨酸含量。
所有研究药物均能降低SBP，但卡托普利对SHR的降压作用最为显著。与对照组相比，SHR左心室中NOS活性和内皮型NOS表达增加。褪黑素和螺内酯进一步增加了NOS表达。通过NF-κB表达和共轭二烯浓度评估的SHR左心室氧化负荷增加。只有褪黑素降低了NF-κB表达并降低了共轭二烯浓度。只有卡托普利减轻了SHR的左心室肥厚，而褪黑素降低了左心室胶原蛋白浓度和羟脯氨酸含量。
得出结论，尽管与卡托普利相比，褪黑素不能逆转左心室肥厚，但它能逆转左心室纤维化。褪黑素的这种保护作用可能是由其显著的抗氧化作用引起的。
