Relaxin and atrial natriuretic peptide pathways participate in the anti-fibrotic effect of a melon
concentrate in spontaneously hypertensive rats
Sammanfattning
Background: In spontaneously hypertensive rats (SHR), a model of human essential
hypertension, oxidative stress is involved in the development of cardiac hypertrophy and fibrosis
associated with hypertension. Dietary supplementation with agents exhibiting antioxidant properties
could have a beneficial effect in remodeling of the heart. We previously demonstrated a potent anti-
hypertrophic effect of a specific melon (Cucumis melo L.) concentrate with antioxidant properties in
spontaneously hypertensive rats. Relaxin and atrial natriuretic peptide (ANP) were reported to reduce
collagen deposition and fibrosis progression in various experimental models.
Objective: The aim of the present investigation was to test the hypothesis that, beside reduction in
oxidative stress, the melon concentrate may act through relaxin, its receptor (relaxin/insulin-like
family peptide receptor 1, RXFP1), and ANP in SHR.
Design and results: The melon concentrate, given orally during 4 days, reduced cardiomyocyte size
(by 25%) and totally reversed cardiac collagen content (Sirius red staining) in SHR but not in their
normotensive controls. Treatment with the melon concentrate lowered cardiac nitrotyrosine-stained
area (by 45%) and increased by 17-19% the cardiac expression (Western blot) of superoxide
dismutase (SOD) and glutathione peroxidase. In addition, plasma relaxin concentration was
normalized while cardiac relaxin (Western blot) was lowered in treated SHR. Cardiac relaxin receptor
level determined by immunohistochemical analysis increased only in treated SHR. Similarly, the
melon concentrate reversed the reduction of plasma ANP concentration and lowered its cardiac
expression.
Conclusions: The present results demonstrate that reversal of cardiac fibrosis by the melon
concentrate involves antioxidant defenses, as well as relaxin and ANP pathways restoration. It is
suggested that dietary SOD supplementation could be a useful additional strategy against cardiac
hypertrophy and fibrosis.