Continuous light and L-NAME-induced left ventricular remodelling: different protection with melatonin and captopril
Abstrakt
Objective Blood pressure enhancement induced by continuous light exposure represents an attractive but rarely investigated model of experimental hypertension. Design and methods The aim of this study was to show whether the combination of continuous light (24 h/day) exposure and chronic N(G)-nitro-L-arginine-methyl ester (L-NAME) treatment induces remodelling of the left ventricle and whether captopril or melatonin can modify these potential alterations.
Six groups of 3-month-old Wistar rats (nine per group) were treated for 6 weeks: control (untreated), L-NAME (40 mg/kg per day), exposed to continuous light, L-NAME treated and exposed to continuous light (L24), L24 rats treated with either captopril 100 mg/kg per day, or melatonin (10 mg/kg/24 h). Systolic blood pressure (SBP), relative weights of the left ventricle, endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) expression in tissues, malondialdehyde and advanced oxidation protein product concentrations in the plasma and hydroxyproline levels in collagenous protein fractions were measured.
Results The continuous light and L-NAME treatment led to hypertension, left ventricular hypertrophy (LVH) and fibrosis. An increase in SBP was completely prevented by captopril and partly by melatonin in the L24 group.
Both drugs reduced oxidative damage and attenuated enhanced expression of ACE in the myocardium. Neither of the drugs prevented the attenuation of eNOS expression in the combined hypertensive model.
Only captopril reduced LVH development in L24, whereas captopril and melatonin reduced left ventricular hydroxyproline concentrations in soluble and insoluble collagen, respectively. The total hydroxyproline concentration was reduced only by melatonin.
Conclusion In hypertension induced by a combination of continuous light and L-NAME treatment, melatonin and captopril protect the heart against pathological left ventricular remodelling differently.