Cocoa shell extract supplementation in hypertensive rats induces outward hypertrophic remodelling in mesenteric resistance arteries, reducing fibrosis

Hypertension is the leading risk factor for cardiovascular diseases and is difficult to control, putting the focus on foods and nutraceuticals. Cocoa has beneficial cardiovascular effects but generates large amounts of residues, such as cocoa shells, which contain bioactive molecules. In a rat model of hypertension (in males) induced by fetal-maternal undernutrition (MUN), supplementation with cocoa shell extract (CSE) at 250 mg/kg for 3 weeks reduced blood pressure, improving mesenteric resistance artery (MRA) vasodilatation. We aimed to investigate, in the same rats, the effect of supplementation on MRA remodelling and stiffening, assessing modifications in cellular and extracellular matrix and contractility. Structural and mechanical parameters were studied with pressure myography, vasoconstriction with wire myography, and cells, collagen and internal elastic lamina fenestrae with confocal microscopy. In comparison to sex-matched control animals, MUN males and females showed a reduction in MRA diameter. However, only MUN males exhibited stiffening, reduced media and increased adventitial layer thickness, and augmented collagen content and noradrenaline-induced contractions. CSE induced outward hypertrophic remodelling, with a normal wall-to-lumen ratio in all groups, and a hypertrophic effect on smooth muscle cells. In addition, in MUN males CSE reduced MRA adventitial collagen and improved elasticity. In conclusion, CSE supplementation induces MRA outward hypertrophic remodelling, possibly related to improved flood flow. In MUN hypertensive rats, the increased diameter and elasticity, associated with modification to the ratio of cells to extracellular matrix, might contribute to the blood pressure-lowering effects of CSE.