The Nitrate-Nitrite-NO Pathway and Its Implications for Heart Failure and Preserved Ejection Fraction

Current Heart Failure Reports
Julio A Chirinos, Payman Zamani

Abstract

The pathogenesis of exercise intolerance in patients with heart failure and preserved ejection fraction (HFpEF) is likely multifactorial. In addition to cardiac abnormalities (diastolic dysfunction, abnormal contractile reserve, chronotropic incompetence), several peripheral abnormalities are likely to be involved. These include abnormal pulsatile hemodynamics, abnormal arterial vasodilatory responses to exercise, and abnormal peripheral O2 delivery, extraction, and utilization. The nitrate-nitrite-NO pathway is emerging as a potential target to modify key physiologic abnormalities, including late systolic left ventricular (LV) load from arterial wave reflections (which has deleterious short- and long-term consequences for the LV), arterial vasodilatory reserve, muscle O2 delivery, and skeletal muscle mitochondrial function. In a recently completed randomized trial, the administration of a single dose of exogenous inorganic nitrate has been shown to exert various salutary arterial hemodynamic effects, ultimately leading to enhanced aerobic capacity in patients with HFpEF. These effects have the potential for both immediate improvements in exercise tolerance and for long-term "disease-modifying" effects. In this review, we provi...Continue Reading

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Citations

Jun 9, 2016·Current Heart Failure Reports·Andrew R Coggan, Linda R Peterson
Sep 12, 2017·European Journal of Heart Failure·Jay N Patel, Sanjiv J Shah
Oct 16, 2016·Journal of the American Heart Association·Julio A ChirinosPayman Zamani
Apr 1, 2017·Circulation Research·Kavita Sharma, David A Kass
Feb 25, 2018·Current Heart Failure Reports·Prabhjot SinghJaved Butler
Mar 12, 2019·Circulation·Anupam A KumarJulio A Chirinos
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Feb 18, 2017·Journal of Cardiovascular Translational Research·Julio A Chirinos
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