Paulis Ludovit, Pechanova Olga, Zicha Josef, Krajcirovicova Kristina, Barta Andrej, Pelouch Vaclav, Adamcova Michaela, Simko Fedor
Center for Cardiovascular Research, Charité-Universitätsmedizin, Berlin, Germany.
J Hypertens Suppl. 2009 Aug;27(6):S11-6. doi: 10.1097/01.hjh.0000358831.33558.97.
Melatonin was shown to reduce blood pressure, enhance nitric oxide availability and scavenge free radicals. There is, however, a shortage of data with respect to the effect of melatonin on pathological left ventricular remodelling associated with haemodynamic overload.
We investigated whether melatonin was able to prevent left ventricular hypertrophy (LVH) and fibrosis associated with N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension.
Four groups of male Wistar rats were investigated: control, L-NAME (50 mg/kg per day), melatonin (10 mg/kg per day) and L-NAME plus melatonin. Blood pressure was measured non-invasively each week. After 5 weeks of treatment the animals were killed and nitric oxide synthase (NOS) activity, endothelial and inducible NOS expression, the level of collagenous proteins, hydroxyproline and conjugated dienes in the left ventricle were determined.
The administration of L-NAME inhibited NOS activity, increased conjugated dienes concentration, elevated blood pressure and induced LVH and fibrosis (indicated by increased collagenous proteins and hydroxyproline levels). The addition of melatonin to L-NAME treatment failed to prevent the attenuation of NOS activity and the development of LVH and prevented hypertension only partly. The administration of melatonin, however, completely prevented the increase in conjugated dienes concentration and the development of left ventricular fibrosis. NOS expression was not different among experimental groups.
Melatonin prevented the development of left ventricular fibrosis and the increase in oxidative load in rats with L-NAME-induced hypertension. The antifibrotic effect of melatonin seems to be independent of its effects on NOS activity and might be linked to its antioxidant properties.
褪黑素已被证明可降低血压、提高一氧化氮可用性并清除自由基。然而，关于褪黑素对与血流动力学过载相关的病理性左心室重构的影响，数据尚不足。
我们研究了褪黑素是否能够预防与N（G）-硝基-L-精氨酸甲酯（L-NAME）诱导的高血压相关的左心室肥厚（LVH）和纤维化。
对四组雄性Wistar大鼠进行了研究：对照组、L-NAME（每天50毫克/千克）、褪黑素（每天10毫克/千克）以及L-NAME加褪黑素组。每周无创测量血压。治疗5周后处死动物，测定左心室内一氧化氮合酶（NOS）活性、内皮型和诱导型NOS表达、胶原蛋白、羟脯氨酸和共轭二烯水平。
给予L-NAME可抑制NOS活性、增加共轭二烯浓度、升高血压并诱导LVH和纤维化（表现为胶原蛋白和羟脯氨酸水平升高）。在L-NAME治疗中添加褪黑素未能预防NOS活性的降低以及LVH的发展，仅部分预防了高血压。然而，给予褪黑素完全预防了共轭二烯浓度的增加和左心室纤维化的发展。各实验组之间NOS表达无差异。
褪黑素预防了L-NAME诱导的高血压大鼠左心室纤维化的发展和氧化负荷的增加。褪黑素的抗纤维化作用似乎与其对NOS活性的影响无关，可能与其抗氧化特性有关。
