{
  "abstract": "Introduction\n\nPrediabetes is increasingly recognised as a stage at which cardiovascular and renal dysfunction begin to develop despite the absence of overt metabolic disease. The mechanisms underlying these early alterations remain poorly understood. Because adipose tissues surrounding blood vessels and kidneys can locally generate components of the renin-angiotensin system (RAS), we hypothesised that subclinical RAS activation contributes to early cardiorenal dysfunction in prediabetes.Methods\n\nUsing a pre-established normotensive, non-obese rat model of prediabetes induced by 12 weeks of mild hypercaloric feeding, we examined the impact of systemic angiotensin II (AngII) elevation and angiotensin-converting enzyme (ACE) inhibition on cardio-, cerebro- and renovascular function by invasive hemodynamics, ex vivo pressure myography, and ex vivo renal perfusion experiments, respectively.Results\n\nPrediabetic rats exhibited impaired parasympathetic baroreceptor sensitivity and altered renovascular endothelium-dependent vasodilation despite preserved blood pressure and cardiac function. Systemic AngII infusion further exacerbated autonomic and renovascular dysfunction. In contrast, treatment with a non-hypotensive dose of the ACE inhibitor captopril restored baroreceptor sensitivity, improved renovascular endothelial function, reduced brainstem inflammation, and attenuated renal tubular fibrosis. Examination of perivascular and perirenal adipose tissues revealed significantly higher protein concentration of ACE1 in prediabetic rats compared to controls.Conclusion\n\nThese findings are consistent with an early activation of RAS contributing to subclinical cardiovascular and renal dysfunction during prediabetes independently of hypertension. Targeting RAS signalling at this early stage may therefore represent a strategy to limit progression of cardiorenal complications along the continuum from prediabetes to diabetes.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.",
    "Department of Pharmacology and Therapeutics, Beirut Arab University, Beirut, Lebanon.",
    "Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar.",
    "Research and Innovation Hub, Alamein International University, Alamein, Egypt.",
    "Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.",
    "Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Nour-Mounira Z Bakkar",
      "orcid": "0000-0002-6403-9348"
    },
    {
      "affs": [
        0
      ],
      "name": "Rana Ghazi"
    },
    {
      "affs": [
        0
      ],
      "name": "Nahed Mougharbil"
    },
    {
      "affs": [
        1
      ],
      "name": "Safaa H Hammoud",
      "orcid": "0000-0001-9418-4071"
    },
    {
      "affs": [
        0
      ],
      "name": "Ramzi Sabra"
    },
    {
      "affs": [
        2
      ],
      "name": "Ali H Eid",
      "orcid": "0000-0003-3004-5675"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Ahmed F El-Yazbi",
      "orcid": "0000-0003-3432-3038"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6r2038na2x5ft.bib",
  "cited_by": 0,
  "doi": "10.1002/edm2.70363",
  "fulltext_url": "https://europepmc.org/articles/PMC13680684",
  "id": "6r2038na2x5ft",
  "issns": [
    "2398-9238"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897734",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2705|Renin-Angiotensin System Studies"
    ]
  ],
  "openalex": "W7223019539",
  "pdf_url": "https://europepmc.org/articles/PMC13680684?pdf=render",
  "pmcid": "PMC13680684",
  "pmid": "42897734",
  "published": "2026-10-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6r2038na2x5ft.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:32Z",
      "native_id": "MED:42897734",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897734"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Renin-Angiotensin System Studies",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Renin-Angiotensin System Activation Drives Early Cardiorenal Dysfunction in Normotensive Prediabetes.",
  "title_text": "Renin-Angiotensin System Activation Drives Early Cardiorenal Dysfunction in Normotensive Prediabetes.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:32Z",
  "url": "https://research.draconitic.com/paper/6r2038na2x5ft",
  "venue": "Endocrinology, diabetes & metabolism",
  "versions": []
}