Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

Abstract

In obstructive sleep apnea (OSA), recurrent obstruction of the upper airway leads to intermittent hypoxia (IH) during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON) or to a group receiving 10 weeks of exercise training (EXE). During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE), whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect.

Nrf2 expression and function, but not MT expression, is indispensable for sulforaphane-mediated protection against intermittent hypoxia-induced cardiomyopathy in mice

“…Zinc has been used extensively to induce MT and prevent various cardiomyopathies [32] , [44] , [45] . Indeed, the importance of zinc availability to protect against IH-induced cardiopathogenesis has been reported recently [46] , [47] , [48] . Therefore, examining whether zinc can be used to induce cardiac MT and protect the heart in patients subject to chronic IH due to OSA may be a worthwhile study.…”

Zinc in Cognitive Impairment and Aging

“…Sleep disorders may induce abnormal reactions in the body, such as oxidative stress, inflammatory response, abnormal hypothalamic-pituitary-adrenal (HPA) axis activity, and abnormal dopamine secretion [ 99 ]. Cognitive impairment due to sleep disorders has also been frequently reported.…”

Prophylactic Zinc Administration Combined with Swimming Exercise Prevents Cognitive-Emotional Disturbances and Tissue Injury following a Transient Hypoxic-Ischemic Insult in the Rat

“…An increasing number of reports have associated the protective effect of zinc with swimming exercise stimulation and improved cell functioning [ 89 , 90 ]. Accordingly, swimming training using MWM protects hippocampal neurons against degenerative changes and improves learning and memory [ 51 ].…”