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Dysfunction in the nitric oxide (NO) signaling pathway can lead to the development of pulmonary hypertension (PH) in mammals. Discovery of an alternative pathway to NO generation involving reduction from nitrate to nitrite and to NO has motivated the evaluation of nitrite as an alternative to inhaled NO for PH. In contrast, inhaled nitrate has not been evaluated to date, and potential benefits include a prolonged half-life and decreased risk of methemoglobinemia. In a canine model of acute hypoxia-induced PH we evaluated the effects of inhaled nitrate to reduce pulmonary arterial pressure (PAP). In a randomized controlled trial, inhaled nitrate was compared to inhaled nitrite and inhaled saline. Exhaled NO, PAP and systemic blood pressures were continuously monitored. Inhaled nitrite significantly decreased PAP and increased exhaled NO. In contrast, inhaled nitrate and inhaled saline did not decrease PAP or increase exhaled NO. Unexpectedly, we found that inhaled nitrite resulted in prolonged (>5 h) exhaled NO release, increase in nitrate venous/arterial levels and a late surge in venous nitrite levels. These findings do not support a therapeutic role for inhaled nitrate in PH but may have therapeutic implications for inhaled nitrite in various disease states.
This article was published in the following journal.
Name: Nitric oxide : biology and chemistry
Hypertension is a multifactorial disease associated with impaired nitric oxide (NO) production and bioavailability. In this respect, restoring NO activity by using nitrite and nitrate has been conside...
The oxygen-independent nitrate-nitrite-nitric oxide (NO) pathway is considered as a substantial source of NO in mammals. Dietary nitrate/nitrite are distributed throughout the body and reduced to NO b...
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An NAD-dependent enzyme that catalyzes the oxidation of nitrite to nitrate. It is a FLAVOPROTEIN that contains IRON and MOLYBDENUM and is involved in the first step of nitrate assimilation in PLANTS; FUNGI; and BACTERIA. It was formerly classified as EC 22.214.171.124.
An iron-sulfur and MOLYBDENUM containing FLAVOPROTEIN that catalyzes the oxidation of nitrite to nitrate. This enzyme can use either NAD or NADP as cofactors. It is a key enzyme that is involved in the first step of nitrate assimilation in PLANTS; FUNGI; and BACTERIA. This enzyme was formerly classified as EC 126.96.36.199.
An enzyme that catalyzes the oxidation of nitrite to nitrate. It is a cytochrome protein that contains IRON and MOLYBDENUM.
An enzyme that catalyzes the oxidation of nitrite to nitrate in the presence of NADP+. It is a FLAVOPROTEIN that contains IRON and MOLYBDENUM. This enzyme was formerly classified as EC 188.8.131.52 and should not be confused with the enzyme NITRATE REDUCTASE (NAD(P)H).
A process facilitated by specialized bacteria involving the oxidation of ammonium to nitrite and nitrate.
Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disorder characterized by abnormally high blood pressure in the arteries between the heart and lungs of affected individuals. Symptoms can range from mild breathles...
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