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.

Hypertension and Cardiovascular Remodelling in Rats Exposed to Continuous Light: Protection by ACE-Inhibition and Melatonin

“…Left ventricular (LV) hypertrophy, although representing an adaptation to hemodynamic overload, is associated with increased cardiovascular risk [1, 2]. The search for new approaches for the prevention or regression of LV hypertrophy in different models of pathological myocardial growth continues [3–7].…”

“…This model of melatonin-deficient hypertension seems to be more physiological than pinealectomy because it reduces only nocturnal melatonin secretion and no surgery is involved [20]. Since melatonin exerts cardiovascular protection on several levels including antioxidant and scavenging actions [21–23], endothelial protection, sympatholytic effect [24–28], and antiarrhythmic effects [29], it is comprehensible that a deficiency of melatonin could result in pathological alterations in circulation and target organ damage [2, 8]. Indeed, several studies with patients suffering from acute myocardial infarction with ST segment elevation indicated that deficit of melatonin could be a negative prognostic factor of the severity of infarction, subsequent remodelling, and prognosis [30–33] and that melatonin supplementation may exert beneficial effects as a radical scavenger in a human model of myocardial ischemia-reperfusion damage [34, 35].…”

Dietary omega-3 fatty acids attenuate myocardial arrhythmogenic factors and propensity of the heart to lethal arrhythmias in a rodent model of human essential hypertension

“…The latter is known to be on rise in the human population. Thus, prevention and successful treatment of hypertension remains of interest to both clinicians and researchers [3][4][5][6]. Thus, prevention and successful treatment of hypertension remains of interest to both clinicians and researchers [3][4][5][6].…”

Can 18F-FDG–PET show differences in myocardial metabolism between Wistar Kyoto rats and spontaneously hypertensive rats?

“…10 However, measurement of regression of left ventricular mass may not be sufficient for the evaluation of the effect of treatment, and an improvement in cardiac metabolism is necessary. 11 Although studies have shown regression of LVH in SHRs after treatment, 12 cardiac metabolism has not been analysed by 18 F-FDG-PET. The importance and relevance of our findings is that analysis of 18 F-FDG uptake by PET could prove useful for evaluating new treatments in the regression of LVH in preclinical studies.…”