Vasoactive Properties of a Cocoa Shell Extract: Mechanism of Action and Effect on Endothelial Dysfunction in Aged Rats

Abstract

Cocoa has cardiovascular beneficial effects related to its content of antioxidant phytochemicals. Cocoa manufacturing produces large amounts of waste, but some by-products may be used as ingredients with health-promoting potential. We aimed to investigate the vasoactive actions of an extract from cocoa shell (CSE), a by-product containing theobromine (TH), caffeine (CAF) and protocatechuic acid (PCA) as major phytochemicals. In carotid and iliac arteries from 5-month and 15-month-old rats, we investigated CSE vasoactive properties, mechanism of action, and the capacity of CSE, TH, CAF and PCA to improve age-induced endothelial dysfunction. Vascular function was evaluated using isometric tension recording and superoxide anion production by dihydroethidium (DHE) staining and confocal microscopy. CSE caused endothelium-dependent vasorelaxation, blocked by L-NAME, but not indomethacin, regardless of sex, age, or vessel type. CSE maximal responses and EC50 were significantly lower compared to acetylcholine (ACh). Arterial preincubation with CSE, TH, CAF or PCA, significantly reduced the number of vascular DHE-positive cells. Compared to adult males, iliac arteries from aged males exhibited reduced ACh concentration-dependent vasodilatation but larger CSE responses. In iliac arteries from aged male and female rats, preincubation with 10−4 M CSE and PCA, but not TH or CAF, improved ACh-relaxations. In conclusion, CSE has vasodilatory properties associated with increased nitric oxide bioavailability, related to its antioxidant phytochemicals, being particularly relevant PCA. Therefore, CSE is a potential food ingredient for diseases related to endothelial dysfunction.

Vascular nitrosative stress in hypertension induced by fetal undernutrition in rats

“…From each litter, some rats were studied at the age of 21 days (weaning) and others at the age of 6 months (adult), using 1-2 rats from each sex and age and the rest of the animals were aged for other studies. We have previously described that MUN male rats develop hypertension by the age of 6 months, assessed either by direct intra-arterial measurement under anesthesia or by tail-cuff plethysmography [33][34][35][36][37][38][39][40][41]. In the present study, tail-cuff plethysmography measurements from adult rats also showed that MUN males had significantly higher systolic blood pressure (SBP) compared to controls (control= 136.9±3.1 mm Hg, n=7; MUN=163.1±3.6, n=8; p=0.004).…”

“…Endothelial function was assessed in iliac arteries by isometric tension recording as previously described [35]. Briefly, 3-mm-long arterial segments were mounted on 168-μm-diameter iron wires and placed on organ bath chambers containing KHS, at 37 °C with carbogen gas (95% O 2 and 5% CO 2 ).…”

“…The iliac artery was used to assess basal levels of superoxide anion generated in the arterial wall by dihydroethidium (DHE; Sigma-Aldrich; USA), as previously described [35]. Briefly, a 4-mm segment of the iliac artery was stabilized in KHS at 37 °C with continuous oxygenation using carbogen gas (95% O 2 and 5% CO 2 ) for 30 min.…”

Onion and Apple Functional Ingredients Intake Improves Antioxidant and Inflammatory Status and Vascular Injury in Obese Zucker Rats

“…In accordance with the results of this study, we have previously shown a significant increase in the NOX activity in arteries obtained from a high-cholesterol-fed rats group, which was significantly reduced in vessels from rats fed the high-cholesterol enriched with onion diet. Also, recently Rodríguez-Rodríguez et al (2022) [ 123 ] indicated the capacity of cocoa shell extract to reduce superoxide anion levels in aged rats. Additionally, Rozentsvit et al (2017) [ 124 ] found the ellagic acid significantly decreased endothelial ROS levels and ameliorated the impairment of vascular relaxation induced by high glucose in Sprague–Dawley rats, suggesting that polyphenols exert a vasculo-protective effect under diabetic conditions via an antioxidant effect that involves inhibition of ERK1/2 and downregulation of NOX4.…”

The Role of By-Products of Fruit and Vegetable Processing for the Dietary Treatment of Cardiovascular Risk Factors: A Narrative Review

“…Endothelial dysfunction is characterized by reduced bioavailability of NO, an important vasodilator molecule produced by endothelial cells [ 35 ]. Typically, reduction in NO bioavailability is associated with increased production of reactive oxygen species and abnormal inflammatory response [ 3 , 27 , 32 , 57 ]. In such circumstances, vascular endothelium is dysfunctional, which can lead to the development of CVD and death [ 3 , 20 , 22 ].…”