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 Szabo, Matthias Karck, Hiromu Sakurai, Gábor Szabó

Research output: Contribution to journalArticle

11 Citations (Scopus)

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
Externally publishedYes

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Acetylcholine
Oxidative Stress
Vasodilation
Nitroprusside
Ventricular Pressure
Baths
Aspirin
Superoxide Dismutase
Endothelium
Anti-Inflammatory Agents
Blood Platelets
Catheters
Antioxidants
Blood Pressure
Pressure
Wounds and Injuries
Therapeutics
copper(II) aspirinate

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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Improvement of aging-associated cardiovascular dysfunction by the orally administered copper(II)-aspirinate complex. / Radovits, Tamás; Gerö, Domokos; Lin, Li Ni; Loganathan, Sivakkanan; Hoppe-Tichy, Torsten; Szabo, Csaba; Karck, Matthias; Sakurai, Hiromu; Szabó, Gábor.

In: Rejuvenation Research, Vol. 11, No. 5, 01.10.2008, p. 945-956.

Research output: Contribution to journalArticle

Radovits, T, Gerö, D, Lin, LN, Loganathan, S, Hoppe-Tichy, T, Szabo, C, Karck, M, Sakurai, H & Szabó, G 2008, 'Improvement of aging-associated cardiovascular dysfunction by the orally administered copper(II)-aspirinate complex', Rejuvenation Research, vol. 11, no. 5, pp. 945-956. https://doi.org/10.1089/rej.2008.0762
Radovits, Tamás ; Gerö, Domokos ; Lin, Li Ni ; Loganathan, Sivakkanan ; Hoppe-Tichy, Torsten ; Szabo, Csaba ; Karck, Matthias ; Sakurai, Hiromu ; Szabó, Gábor. / Improvement of aging-associated cardiovascular dysfunction by the orally administered copper(II)-aspirinate complex. In: Rejuvenation Research. 2008 ; Vol. 11, No. 5. pp. 945-956.
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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.",
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T1 - Improvement of aging-associated cardiovascular dysfunction by the orally administered copper(II)-aspirinate complex

AU - Radovits, Tamás

AU - Gerö, Domokos

AU - Lin, Li Ni

AU - Loganathan, Sivakkanan

AU - Hoppe-Tichy, Torsten

AU - Szabo, Csaba

AU - Karck, Matthias

AU - Sakurai, Hiromu

AU - Szabó, Gábor

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N2 - 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.

AB - 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.

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