Effects of the copper(II) aspirinate complex on cardiovascular dysfunction associated with aging

Abstract

Overproduction of free radicals in aging tissues causes nitro-oxidative stress and molecular inflammatory reactions, which play an important role in the pathogenesis of cardiovascular dysfunction associated with aging. It has been reported, that the copper(II) aspirinate complex (CuAsp) exerts not only the anti-inflammatory and platelet anti-aggregating effects of aspirin, but due to its superoxide dismutase mimetic activity, it acts as an antioxidant as well. In this study we investigated the effects of CuAsp on aging-associated cardiovascular dysfunction. Aging (24 months) and young (3 months) rats were treated for 3 weeks with vehicle, or with CuAsp (200 mg/kg/day). Left ventricular pressure–volume (PV) relations were measured by using a microtip Millar PV conductance catheter, and indexes of contractility (e.g. slope of ESPVR (Emax)) were calculated. In organ bath experiments for isometric tension endothelium-dependent and -independent vasorelaxation of isolated aortic rings were investigated by using acetylcholine (ACh) and sodium nitroprusside (SNP). When compared to the young controls, aging rats showed impaired left ventricular contractility (Emax: 0.51±0.04 vs. 2.16±0.28 mm Hg/μl; p<0.05) and a marked endothelial dysfunction (max. relaxation to ACh: 66.66±1.30 vs. 87.09±1.35%; p<0.05). Treatment with CuAsp resulted in a significantly improved cardiac function (Emax: 1.21±0.17 vs. 0.51±0.04 mm Hg/μl) and higher vasorelaxation to ACh in aging rats (94.83±0.73 vs. 66.66±1.30%). The treatment did not influence the cardiovascular functions of young rats. 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.