{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T16:20:05Z","timestamp":1783095605519,"version":"3.54.6"},"reference-count":68,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Fetal undernutrition establishes the foundations for hypertension development, with oxidative stress being a key hallmark. A growing interest in nutraceuticals for treating hypertension and environmental waste concerns prompted the present study aiming to evaluate whether supplementation with a polyphenol enriched extract from cocoa shell (CSE), a by\u2010product from the chocolate industry with antioxidant properties, reduces hypertension of developmental origin, thus improving mesenteric resistance artery (MRA) vasodilatation. Adult male and female offspring from rats exposed to 50% food restriction from mid\u2010gestation (maternal undernutrition, MUN) and controls were used. Supplementation was given through a gelatine (vehicle, VEH) or containing CSE (250\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>\u00a0day<jats:sup>\u22121<\/jats:sup>) 5\u00a0days\u00a0week<jats:sup>\u22121<\/jats:sup>for 3\u00a0weeks. Systolic blood pressure (SBP) was assessed by tail\u2010cuff plethysmography. MRA function was studied by wire myography, and superoxide anion and nitric oxide were investigated by fluorescent indicators and confocal microscopy. Compared to control\u2010VEH, MUN\u2010VEH males showed significantly higher SBP, reduced MRA as well as relaxation to ACh, sodium nitroprusside and the AMPK agonist 5\u2010aminoimidazole\u20104\u2010carboxamide riboside, but not to isoproterenol. In MUN males, endothelial endothelium\u2010derived hyperpolarizing factor and nitric oxide were unaltered, but MRA released a vasoconstrictor prostanoid and produced higher levels of superoxide anion. CSE normalized blood pressure and improved all above\u2010mentioned MRA alterations in MUN males without an effect on control counterparts, except the reduction of superoxide anion. MUN\u2010VEH females were normotensive and only showed a tendency towards larger superoxide anion production, which was abolished by CSE. CSE supplementation reduces SBP improving endothelium\u2010dependent and independent MRA vasodilatation, related to local superoxide anion reduction, being a potential nutraceutical ingredient to counteract hypertension, in addition to contributing to the circular economy.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16346-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>Fetal undernutrition induces hypertension in males associated with deficient resistance artery vasodilatation, being normalized by cocoa shell extract (CSE).<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Release of a cyclooxygenase\u2010derived contractile factor is the main endothelial alteration, which is abolished by CSE.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>AMPK and soluble guanylyl cyclase\u2010mediated relaxation are also reduced in smooth muscle cells from maternal undernutrition resistance arteries, being improved by CSE.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Vascular oxidative damage caused by excess superoxide anion generation can account for impaired vasodilatation, which is improved by CSE.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>The capacity of CSE to improve relaxation is probably related to its antioxidant bioactive factors, and thus cocoa shell is a potential food by\u2010product to treat hypertension.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp287097","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T15:59:48Z","timestamp":1728575988000},"page":"6065-6085","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Resistance artery vasodilator pathways involved in the antihypertensive effects of cocoa shell extract in rats exposed to fetal undernutrition"],"prefix":"10.1113","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2216-5335","authenticated-orcid":false,"given":"Santiago","family":"Ruvira","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Universidad Aut\u00f3noma de Madrid Madrid Spain"},{"name":"Food, Oxidative Stress and Cardiovascular Health (FOSCH) Research Group Universidad Aut\u00f3noma de Madrid Madrid 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