{
  "abstract": "Introduction Essential arterial hypertension (AH) presents a significant global health challenge, characterised not only by its widespread prevalence but also by its detrimental effects on target organs over time. Contemporary management strategies for AH increasingly prioritise the prevention and reversal of structural remodelling in vital organs, in addition to achieving blood pressure (BP) reduction. Central to the pathophysiology of hypertension is endothelial dysfunction, particularly the deficiency of nitric oxide (NO), which is recognised as a critical mechanism underlying this condition. This study aims to investigate the consequences of inhibiting NO synthesis on cardiovascular and extracardiac organs, while also evaluating the potential of various antihypertensive drug classes to reverse these pathological changes.Methods A total of sixty-three male rats were subjected to L-NAME–induced hypertension through an intraperitoneal injection of 40 mg/kg over a duration of 7 weeks. Between weeks 5 and 7, the rats were treated with one of the following interventions: Nebivolol Plus, Losartan Plus, Amlodipine combined with hydrochlorothiazide (HCTZ), HCTZ alone, or L-arginine. Blood pressure measurements were conducted using the tail-cuff method. Additionally, levels of arterial and venous nitric oxide (NO) metabolites (NOx) were assessed via the Griess method, while endothelin-1 levels were quantified using ELISA. Histological examinations were performed on the hearts, kidneys, brains, and carotid arteries. Statistical analysis was carried out using Student’s t-test and Pearson correlation coefficients, with a significance threshold set at p<0.05.Results L-NAME administration resulted in a sustained increase in both systolic and diastolic blood pressure (SBP, DBP), accompanied by an irreversible reduction in arterial and venous NO levels. A significant correlation was identified between NO levels and (SBP-DBP), suggesting a functional relationship between NO deficiency and hemodynamic changes. Despite the size of the organs remaining relatively stable, notable pathological alterations were observed, including left ventricular hypertrophy, renal vascular congestion, focal haemorrhages, and early sclerosis. These changes persisted even after the discontinuation of L-NAME.Therapeutic intervention during the final 3 weeks produced differential outcomes. Nebivolol Plus, Losartan Plus, and Norvasc + HCTZ effectively reduced BP (≈39–42%) and substantially increased NO concentrations (arterial: +40–70%; venous: +20–30%). These treatments also reduced carotid wall thickness (18–24%) and promoted regression of cardiac and renal vascular lesions. In contrast, HCTZ monotherapy produced weaker BP lowering and minimal NO restoration, without improvement in carotid structure.L-arginine has shown significant effectiveness in normalising blood pressure, while also modestly enhancing NO levels and reducing carotid artery thickness by 27%. Importantly, all treatments, except for HCTZ, contributed to a regression of left ventricular hypertrophy and renal vascular lesions. This underscores their potential in promoting overall cardiovascular health.Conclusions/Implications Endothelial dysfunction is central to the structural remodelling of target organs in NO-deficient hypertension. Nebivolol, unlike traditional assumptions regarding beta-blockers, demonstrated strong endothelial-protective and organ-remodelling effects comparable to RAAS blockade and calcium channel inhibition. Findings support a differentiated view of beta-blockers as a heterogeneous class and highlight nebivolol as a promising early-stage therapeutic option, including asymptomatic AH, particularly when endothelial dysfunction is evident.",
  "authors": [
    {
      "affiliations": [
        "Tbilisi State Medical University, Tbilisi, Georgia"
      ],
      "name": "Tamar Sanikidze"
    },
    {
      "affiliations": [
        "Georgian National University, Tbilisi, Georgia"
      ],
      "name": "Maka Buleishvili"
    },
    {
      "affiliations": [
        "BAU International University Batumi, Batumi, Georgia"
      ],
      "name": "Irina Imerlishvili"
    },
    {
      "affiliations": [
        "Tbilisi State Medical University, Tbilisi, Georgia"
      ],
      "name": "Ketevan Kakabadze"
    }
  ],
  "title": "18 Endothelial dysfunction–driven organ remodelling in L-NAME-induced hypertension and its reversal by antihypertensive therapy in rats",
  "uid": "902f3c42-6f25-51bb-b0a7-de237f44ea57"
}