Abstract
Fatty acid (FA)‐derived lipid products generated by cytochrome P450 (CYP), lipoxygenase (LOX), and cyclo‐oxygenase (COX) influence cardiovascular function. However, plasma measurements invariably ignore 40% of the blood specimen, namely the erythrocytes. These red blood cells (RBCs) represent a cell mass of about 3 kg. RBCs are a potential reservoir for epoxy fatty acids, which on release could regulate vascular capacity. We tested the hypothesis that maximal physical activity would influence the epoxy fatty acid status in RBCs. We used a standardized maximal treadmill exercise according to Bruce to ensure a robust hemodynamic and metabolic response. Central hemodynamic monitoring was performed using blood pressure and heart rate measurements and maximal workload was assessed in metabolic equivalents (METs). We used tandem mass spectrometry (LC‐MS/MS) to measure epoxides derived from CYP monooxygenase, as well as metabolites derived from LOX, COX, and CYP hydroxylase pathways. Venous blood was obtained for RBC lipidomics. With the incremental exercise test, increases in the levels of various CYP epoxy‐mediators in RBCs, including epoxyoctadecenoic acids (9,10‐EpOME, 12,13‐EpOME), epoxyeicosatrienoic acids (5,6‐EET, 11,12‐EET, 14,15‐EET), and epoxydocosapentaenoic acids (16,17‐EDP, 19,20‐EDP) occurred, as heart rate, systolic blood pressure, and plasma lactate concentrations increased. Maximal (13.5 METs) exercise intensity had no effect on diols and various LOX, COX, and hydroxylase mediators. Our findings suggest that CYP epoxy‐metabolites could contribute to the cardiovascular response to maximal exercise.
Highlights
Optimal exercise performance requires an integrated organ system response
red blood cells (RBCs) (~3 kg in human body) have been implicated to serve as a reservoir for epoxide fatty acids, in particular cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs), which on release may act in a vasoregulatory capacity (Jiang et al, 2010; Jiang et al, 2011)
The data suggest that exercise leads to an accumulation of various CYP epoxy-metabolites into membrane-bound compartments of RBCs under exhaustive exercise or in ischemia in healthy individuals, which on release may act in a vasoregulatory capacity
Summary
Optimal exercise performance requires an integrated organ system response. The entire cardiovascular system, pulmonary, systemic circulations enable increased gas exchange and oxygen availability to exercising muscles. The net effect of acute systemic hypoxia in quiescent skeletal muscle is vasodilation that occurs despite significant reflex increases in muscle sympathetic nerve activity. This vasodilation increases tissue perfusion and oxygen delivery to maintain tissue oxygen consumption (Dinenno, 2016). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
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