Relaxin and atrial natriuretic peptide pathways participate in the anti-fibrotic effect of a melon concentrate in spontaneously hypertensive rats

La relaxine et le peptide natriurétique atrial participent à l'effet anti-fibrotique d'un concentré de melon chez le rat spontanément hypertendu.

Julie Carillon (1) , Audrey Gauthier (1) , Sandy Barial (1) , Michel Tournier (2, 1) , Nathalie Gayrard (1) , Anne-Dominique Lajoix (2, 1) , Bernard Jover (3, 1)

1 BC2M - Biocommunication en Cardio-Métabolique
2 CPID - Centre de pharmacologie et innovation dans le diabète
3 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]

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 17Á19% 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.

Mots clés: Cardiomyocyte; Relaxin/insulin-like family peptide receptor 1; Endogenous antioxidant defense; Fibrosis; Oxidative stress

Domaines: Alimentation et Nutrition; Cardiologie et système cardiovasculaire

Julie Carillon, Audrey Gauthier, Sandy Barial, Michel Tournier, Nathalie Gayrard, et al.. Relaxin and atrial natriuretic peptide pathways participate in the anti-fibrotic effect of a melon concentrate in spontaneously hypertensive rats. Food and Nutrition Research, 2016, 60, pp.30985. ⟨10.3402/fnr.v60.30985⟩. ⟨hal-01615225⟩