Original ContributionActive secretion and protective effect of salivary nitrate against stress in human volunteers and rats
Graphical abstract
Highlights
► Active secretion of salivary nitrate is one of the human adaptive responses to stress. ► Salivary nitrate and its derivates can prevent stress-induced gastric ulcer. ► Salivary nitrate and its derivates restore blood flow in the stomach mucosa. ► The nitrate–nitrite–NO pathway may contribute to stress-injury protection.
Section snippets
Human bungee jump protocol
Twenty-two healthy volunteers naive to bungee jumping or skydiving (14 males and 8 females, age range 21–45 years, mean age 27 years) were involved in the human stress trial. All volunteers had been living in Beijing, China, for more than 1 year and shared similar dietary habits. The trial was reviewed and approved by the ethics committees of Capital Medical University of China. Written informed consent was obtained from all subjects.
All subjects participated in a bungee jump from a height of 68
Primary physical indexes significantly changed after acute stress
To confirm the stress status of each subject, primary physical indexes, including breath, pulse, systolic pressure, diastolic pressure, plasma adrenalin, and plasma noradrenalin were determined 3 h before and immediately after the jump. The average frequency of breaths increased from 15±4 to 23±6 per minute (p<0.001) and the average pulse rate increased from 67±8 to 114±20 per minute (p<0.001, Fig. 1A and 1B). Blood pressure increased in a similar fashion (p<0.001, Figs. 1C and 1D). The average
Discussion
In this study, we found that the levels of salivary nitrate and nitrite were immediately increased in human volunteers after a strong acute stress caused by high-platform jumping. To explore the biological function of salivary nitrate and nitrite, we carried out a rat WIRS assay. We found that blocking nitrate secretion from the salivary glands results in a significant decrease in gastric mucosal blood flow and increased gastric ulcers in rats treated by BPSDL, which leads to >60% decreases in
Acknowledgments
This study was supported by grants from the National Natural Science Foundation of China (30430690, 30125042, and 81170975) and Beijing Municipal Committee for Science and Technology (Z121100005212004). The authors acknowledge the volunteers who participated in this study.
References (38)
Role of N-nitroso compounds (NOC) and N-nitrosation in etiology of gastric, esophageal, nasopharyngeal and bladder cancer and contribution to cancer of known exposures to NOC
Cancer Lett.
(1995)- et al.
The effect of dietary nitrate on salivary plasma and urinary nitrate metabolism in humans
Free Radic. Biol. Med.
(2003) - et al.
Intragastric generation of antimicrobial nitrogen oxides from saliva—physiological and therapeutic considerations
Free Radic. Biol. Med.
(2006) - et al.
Protection from nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers by dietary nitrate
Free Radic. Biol. Med.
(2007) - et al.
The effects of drugs on the stress ulcer in rats
Jpn. J. Pharmacol.
(1968) - et al.
Dietary inorganic nitrate improves mitochondrial efficiency in humans
Cell Metab.
(2011) - et al.
The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash
Nitric Oxide
(2008) - et al.
Inorganic nitrate is a possible source for systemic generation of nitric oxide
Free Radic. Biol. Med.
(2004) - et al.
Recurrent swelling of parotid gland and Sjögren's syndrome
Int. J. Oral Maxillofac. Surg.
(1993) - et al.
Nitrate and gastric cancer risks
Nature
(1985)
Progression of gastric cancer etiology: N-nitrosamides in the 1990s
World J. Gastroenterol.
Nitrate synthesis in the germfree and conventional rat
Science
Destruction of parotid glands affects nitrate and nitrite metabolism
J. Dent. Res.
Alterations of nitrate and nitrite content in saliva, serum, and urine in patients with salivary dysfunction
J. Oral Pathol. Med.
Dietary nitrate in man: friend or foe?
Br. J. Nutr.
The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics
Nat. Rev. Drug Discovery
Effects of dietary nitrate on blood pressure in healthy volunteers
N. Engl. J. Med.
Stomach NO synthesis
Nature
A mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis
Nat. Chem. Biol.
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These authors contributed equally to this work.