Improvement of aging-associated cardiovascular dysfunction by the orally administered copper(II)-aspirinate complex

Tamás Radovits, Domokos Gerö, Li Ni Lin, Sivakkanan Loganathan, Torsten Hoppe-Tichy, Csaba Szabó, Matthias Karck, Hiromu Sakurai, Gábor Szabó

    Research output: Contribution to journalArticle

    11 Scopus citations

    Abstract

    Background: Aging-associated nitro-oxidative stress causes tissue injury and activates proinflammatory pathways that play an important role in the pathogenesis of aging-associated cardiovascular dysfunction. It has been recently reported, that the copper(II)-aspirinate complex (CuAsp) exerts not only the well-known anti-inflammatory and platelet antiaggregating effects of aspirin, but, due to its superoxide dismutase mimetic activity, it acts as a potent antioxidant as well. In this study we investigated the effects of CuAsp on aging-associated myocardial and endothelial dysfunction. Methods and Results: Aging and young rats were treated for 3 weeks with vehicle, or with CuAsp (200 mg/kg per day per os). Left ventricular pressure-volume relations were measured by using a microtip pressure-volume conductance catheter, and indexes of contractility (e.g., slope of end-systolic pressure-volume relationships [ESPVR] [Ees], and dP/dtmax - end-diastolic volume [EDV]) were calculated. In organ bath experiments for isometric tension with isolated aortic rings, endothelium-dependent and -independent vasorelaxation were investigated by using acetylcholine and sodium nitroprusside. When compared to the young controls, aging rats showed impaired left ventricular contractility (E es, 0.51 ± 0.04 vs. 2.16 ± 0.28 mmHg/μL; dP/dt max - EDV, 10.71 ± 2.02 vs. 37.23 ± 4.18 mmHg/sec per μL; p < 0.05) and a marked endothelial dysfunction (maximal relaxation to acetylcholine: 66.66 ± 1.30 vs. 87.09 ± 1.35%; p < 0.05). Treatment with CuAsp resulted in reduced nitro-oxidative stress, improved cardiac function (Ees, 1.21 ± 0.17 vs. 0.51 ± 0.04 mmHg/μL; dP/dtmax - EDV, 23.40 ± 3.34 vs. 10.71 ± 2.02 mmHg/sec per μL; p < 0.05) and higher vasorelaxation to acetylcholine in aging animals (94.83 ± 0.73 vs. 66.66 ± 1.30%; p < 0.05). The treatment did not influence the cardiovascular functions of young rats. Conclusions: Our results demonstrate that oxidative stress and inflammatory pathways contribute to the pathogenesis of cardiovascular dysfunction in the aging organism, which can be reversed by CuAsp.

    Original languageEnglish (US)
    Pages (from-to)945-956
    Number of pages12
    JournalRejuvenation Research
    Volume11
    Issue number5
    DOIs
    StatePublished - Oct 1 2008

      Fingerprint

    ASJC Scopus subject areas

    • Aging
    • Geriatrics and Gerontology

    Cite this

    Radovits, T., Gerö, D., Lin, L. N., Loganathan, S., Hoppe-Tichy, T., Szabó, C., Karck, M., Sakurai, H., & Szabó, G. (2008). Improvement of aging-associated cardiovascular dysfunction by the orally administered copper(II)-aspirinate complex. Rejuvenation Research, 11(5), 945-956. https://doi.org/10.1089/rej.2008.0762