Nitrate and nitrite are commonly thought of as inert end products of nitric oxide (NO) oxidation, possibly carcinogenic food additives, or well-water contaminants. However, recent studies have shown that nitrate and nitrite play an important role in cardiovascular and gastrointestinal homeostasis through conversion back into NO via a physiological system involving enterosalivary recirculation, bacterial nitrate reductases, and enzyme-catalyzed or acidic reduction of nitrite to NO. The diet is a key source of nitrate in adults; however, infants ingest significantly less nitrate due to low concentrations in breast milk. In the mouth, bacteria convert nitrate to nitrite, which has gastro-protective effects. However, these nitrate-reducing bacteria are relatively inactive in infants. Swallowed nitrite is reduced to NO by acid in the stomach, affecting gastric blood flow, mucus production, and the gastric microbiota. These effects are likely attenuated in the less acidic neonatal stomach. Systemically, nitrite acts as a reservoir of NO bioactivity that can protect against ischemic injury, yet plasma nitrite concentrations fall dramatically at birth and remain markedly lower than in adults for the first few weeks of life. The physiological importance of the diminished nitrate→nitrite→NO axis in infants and its implications in the etiology and treatment of newborn diseases such as necrotizing enterocolitis and hypoxic/ischemic injury are yet to be determined.

LLU Discipline



Basic Sciences


School of Medicine

First Advisor

Blood, Arlin B.

Second Advisor

Hopper, Andrew

Third Advisor

Patel, Rakesh

Fourth Advisor

Power, Gordon

Fifth Advisor

Zhang, Lubo

Degree Name

Doctor of Philosophy (PhD)

Degree Level


Year Degree Awarded


Date (Title Page)




Library of Congress/MESH Subject Headings

Infant - Newborn; Infant Nutritional Physiological Phenomena; Homeostasis; Diet; Milk - Human; Infant Formula; Nitrates - Metabolism; Nitrites - Metabolism; Saliva - Metabolism; Gastrointestional Tract

Subject - Local

Nitric Oxide Oxidation; Cardiovascular Homeostasis; Gastrointestinal Homeostasis; Enterosalivary recirculation; Bacterial Nitrate Reductases; Gastro-protective Effects;



Page Count


Digital Format


Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.


Loma Linda University Electronic Theses and Dissertations

Collection Website



Loma Linda University. Del E. Webb Memorial Library. University Archives