Remodelling of the heart and vessels in experimental hypertension: advances in protection

Abstract

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.