Department of Pathophysiology, School of Medicine, Comenius University, Sasinkova 4, Bratislava, Slovak Republic.
J Hypertens. 2010 Sep;28 Suppl 1:S1-6. doi: 10.1097/01.hjh.0000388487.43460.db.
Left ventricular hypertrophy (LVH), despite its adaptive nature, increases cardiovascular morbidity and mortality. Novel approaches for protection against pathological heart remodelling are presented in this supplement. Melatonin diminishes myocardial fibrosis in rats exposed to continuous light and N-nitro-L-arginine-methyl ester (L-NAME) treatment and reduces production of endothelium-derived constricting factors in L-NAME-induced hypertension. Melatonin, because of its extraordinary antioxidant and scavenging properties, benefits for endothelium and sympatholytic action, may prove to be a useful protective drug against heart remodelling. In hypertension induced by relative aldosteronism, the correction of macro and micronutrient dyshomeostasis appears to act beneficially within pathological myocardial remodelling. Alterations in the signal cascade of pathological myocardial growth, including humoral stimuli, receptors, intracellular messengers or transcriptional factors, may be favourably modified at different levels. Inhibition of nuclear factor kappa B (NF-kappaB) potentiates hypertension development, enhances oxidative load, increases the cross-sectional area of the aorta and reduces nitric oxide (NO) synthase activity in L-NAME hypertension. It is suggested that NF-kappaB may play a protective rather than a deleterious role in the haemodynamically overloaded circulation. Compound 21, a recently developed peptide angiotensin II type 2 (AT2) receptor agonist, offers a novel approach in investigating the role of AT2 receptors in the protection of the hypertensive heart. A novel NO donor, L-419, with its intrinsic protection of NO, improves the entire NO signalling cascade and thus favourably influencing the response of the left ventricle to haemodynamic overload. LVH prevention or regression should be considered a therapeutic success only when, along with hypertrophied mass reduction, an improvement of the heart structure, function, metabolism and electrical stability is achieved.
左心室肥厚（LVH）尽管具有适应性，但会增加心血管发病率和死亡率。本增刊介绍了预防病理性心脏重构的新方法。褪黑素可减少暴露于连续光照和 N-硝基-L-精氨酸甲酯（L-NAME）治疗的大鼠的心肌纤维化，并减少 L-NAME 诱导的高血压中内皮衍生收缩因子的产生。褪黑素由于其非凡的抗氧化和清除特性，对内皮有益，具有交感神经抑制作用，可能被证明是一种有用的抗心脏重构保护药物。在相对醛固酮增多症引起的高血压中，纠正宏量和微量营养素的稳态失调似乎在病理性心肌重构中具有有益作用。病理性心肌生长的信号级联改变，包括体液刺激物、受体、细胞内信使或转录因子，可能在不同水平上得到有利的修饰。核因子 kappa B（NF-kappaB）的抑制可增强高血压的发展，增加氧化负荷，增加 L-NAME 高血压中主动脉的横截面积并降低一氧化氮（NO）合酶活性。有人提出，NF-kappaB 在血流动力学超负荷循环中可能发挥保护作用而不是有害作用。最近开发的肽血管紧张素 II 型 2（AT2）受体激动剂化合物 21 为研究 AT2 受体在保护高血压心脏中的作用提供了一种新方法。一种新型的一氧化氮供体 L-419 具有其内在的一氧化氮保护作用，可改善整个一氧化氮信号级联，从而有利地影响左心室对血流动力学超负荷的反应。只有当肥厚质量减少的同时，还改善了心脏结构、功能、代谢和电稳定性，才能将 LVH 的预防或逆转视为治疗成功。
