Preprint Article Version 1 This version is not peer-reviewed

NOX Inhibition Improves β Adrenergic-Stimulated Contractility and Intracellular Calcium Handling in the Aged Heart

Version 1 : Received: 13 April 2018 / Approved: 16 April 2018 / Online: 16 April 2018 (06:17:57 CEST)

How to cite: Valdés, A.; Barrios, G.; Ponce, N.; Dulce, R.A.; Gonzalez, D.R. NOX Inhibition Improves β Adrenergic-Stimulated Contractility and Intracellular Calcium Handling in the Aged Heart. Preprints 2018, 2018040190 (doi: 10.20944/preprints201804.0190.v1). Valdés, A.; Barrios, G.; Ponce, N.; Dulce, R.A.; Gonzalez, D.R. NOX Inhibition Improves β Adrenergic-Stimulated Contractility and Intracellular Calcium Handling in the Aged Heart. Preprints 2018, 2018040190 (doi: 10.20944/preprints201804.0190.v1).

Abstract

Cardiac aging is characterized by alterations in contractility and intracellular calcium ([Ca2+]i) homeostasis. It has been suggested that oxidative stress may be involved in this process. We and others have reported that in cardiomyopathies the NADPH oxidase (NOX)-derived superoxide is increased, with a negative impact on [Ca2+]i and contractility. We tested the hypothesis that in the aged heart, [Ca2+]i handling and contractility are disturbed by NOX-derived superoxide. Contractility was evaluated isolated hearts, challenged with isoproterenol. To assess [Ca2+]i, isolated cardiac myocytes were field-stimulated and [Ca2+]i was monitored with fura-2. Cardiac concentration-response to isoproterenol was depressed in aged compared to adults hearts (p < 0.005), but was restored by NOX inhibitors apocynin and VAS2870. In isolated cardiomyocytes, apocynin increased the amplitude of [Ca2+]i in aged myocytes (p < 0.05). Time-50 [Ca2+]i decay was increased in aged myocytes (p < 0.05) and reduced towards normal by NOX inhibition. In addition, we found that myofilaments Ca2+ sensitivity was reduced in aged myocytes (p < 0.05), and further reduced by apocynin. Finally SERCA levels but not phospholamban were reduced in aged hearts (p < 0.05). In conclusion, β-adrenergic‒induced contractility was depressed in aged hearts, and NOX inhibition restored back to normal. Moreover, altered Ca2+ handling in aged myocytes was also improved by NOX inhibition. These results suggest a NOX-dependent effect in aged myocytes at the level of Ca2+ handling proteins and myofilaments.

Subject Areas

NADPH oxidases; apocynin; VAS2870; aged heart; cardiomyocytes; isoproterenol; TBARS

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