{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:06:39Z","timestamp":1773288399900,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,6,5]],"date-time":"2021-06-05T00:00:00Z","timestamp":1622851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"1) Ministerio de Ciencia, Innovaci\u00f3n y Universidades from Spain  and 2) FCT\/MCTES, Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia and Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior","award":["RTI2018-097504-B-I00 and UIDB\/50006\/2020"],"award-info":[{"award-number":["RTI2018-097504-B-I00 and UIDB\/50006\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Fetal undernutrition is a risk factor for cardiovascular diseases. Male offspring from rats exposed to undernutrition during gestation (MUN) exhibit oxidative stress during perinatal life and develop cardiac dysfunction in ageing. Angiotensin-II is implicated in oxidative stress-mediated cardiovascular fibrosis and remodeling, and lactation is a key developmental window. We aimed to assess if alterations in RAS during lactation participate in cardiac dysfunction associated with fetal undernutrition. Control dams received food ad libitum, and MUN had 50% nutrient restriction during the second half of gestation. Both dams were fed ad libitum during lactation, and male offspring were studied at weaning. We assessed: ventricular structure and function (echocardiography); blood pressure (intra-arterially, anesthetized rats); collagen content and intramyocardial artery structure (Sirius red, Masson Trichromic); myocardial and intramyocardial artery RAS receptors (immunohistochemistry); plasma angiotensin-II (ELISA) and TGF-\u03b21 protein expression (Western Blot). Compared to Control, MUN offspring exhibited significantly higher plasma Angiotensin-II and a larger left ventricular mass, as well as larger intramyocardial artery media\/lumen, interstitial collagen and perivascular collagen. In MUN hearts, TGF-\u03b21 tended to be higher, and the end-diastolic diameter and E\/A ratio were significantly lower with no differences in ejection fraction or blood pressure. In the myocardium, no differences between groups were detected in AT1, AT2 or Mas receptors, with MrgD being significantly lower in the MUN group. In intramyocardial arteries from MUN rats, AT1 and Mas receptors were significantly elevated, while AT2 and MrgD were lower compared to Control. Conclusions. In rats exposed to fetal undernutrition, RAS disbalance and associated cardiac remodeling during lactation may set the basis for later heart dysfunction.<\/jats:p>","DOI":"10.3390\/pathophysiology28020018","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T22:23:00Z","timestamp":1623104580000},"page":"273-290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Implication of RAS in Postnatal Cardiac Remodeling, Fibrosis and Dysfunction Induced by Fetal Undernutrition"],"prefix":"10.3390","volume":"28","author":[{"given":"Pilar","family":"Rodr\u00edguez-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"FOSCH Group, Department of Physiology, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2750-4746","authenticated-orcid":false,"given":"Maria Sof\u00eda","family":"Vieira-Rocha","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Bego\u00f1a","family":"Quintana-Villamandos","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Hospital Universitario Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"},{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6370-0467","authenticated-orcid":false,"given":"Ignacio","family":"Monedero-Cobeta","sequence":"additional","affiliation":[{"name":"FOSCH Group, Department of Physiology, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}]},{"given":"Parichat","family":"Prachaney","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Group, Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}]},{"given":"Angel Luis","family":"L\u00f3pez de Pablo","sequence":"additional","affiliation":[{"name":"FOSCH Group, Department of Physiology, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5522-0786","authenticated-orcid":false,"given":"Maria del Carmen","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"FOSCH Group, Department of Physiology, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9509-0613","authenticated-orcid":false,"given":"Manuela","family":"Morato","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-9360","authenticated-orcid":false,"given":"Carmen","family":"Diniz","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Silvia M.","family":"Arribas","sequence":"additional","affiliation":[{"name":"FOSCH Group, Department of Physiology, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1136\/heart.84.6.595","article-title":"Coronary heart disease after prenatal exposure to the Dutch famine, 1944\u201345","volume":"84","author":"Roseboom","year":"2000","journal-title":"Heart"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1177\/1933719109349536","article-title":"Maternal Vitamin D Deficiency Leads to Cardiac Hypertrophy in Rat Offspring","volume":"17","author":"Gezmish","year":"2009","journal-title":"Reprod. 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