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

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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
Pages (from-to)945-956
Number of pages12
JournalRejuvenation Research
Volume11
Issue number5
DOIs
Publication statusPublished - Oct 1 2008

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ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

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