Improvement of Aging-Associated Cardiovascular Dysfunction by the Orally Administered Copper(II)-Aspirinate Complex

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] [E es ], and dP/dt max Ϫ 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 Ϯ 0.04 vs. 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.

Diabetes and Age-Related Differences in Vascular Function of Renal Artery: Possible Involvement of Endoplasmic Reticulum Stress

“…[1][2][3][4] There is an emerging body of evidence suggesting that diabetes and/or aging result in abnormal vascular functions, including impaired relaxation and augmented contraction. [4][5][6][7] For example, contractions induced by endothelium-derived contracting factor (EDCF) contribute to endothelial dysfunction in various animal models of aging, diabetes, and cardiovascular diseases.…”

Green Synthesis of Copper Triflusalate and Pyridine Adducts

“…Metallopharmaceutics, often involving zinc or copper, can play critical roles in the normal functioning of damaged organisms by achieving specific release at target locations . For some common drugs involving functional ester groups susceptible to hydrolysis, such as aspirin, the complexation with Cu(II) has been reported to enhance the activity, while reducing gastrointestinal side effects . Contrarily, the pronounced tendency of the triflusal ester group to hydrolysis in water and alcoholic solutions, likely explains the lack of reported metal coordination complexes for this molecule.…”

Enhancement of Myocardial and Vascular Function after Phosphodiesterase-5 Inhibition in a Rat Model

“…A frequently used parameter for myocardial contractility is peak positive dP/dt. 7,[20][21][22][23][24] Unfortunately, many contractility parameters including peak positive dP/dt as well as other contractility parameters (ejection fraction, cardiac output, and SW) are strongly load dependent and as such unable to reveal positive inotropic effects in drugs having a marked vasodilative and thereby load-reducing effect. 16 .…”