Scientists have long known that the blood pressure drops after exercise but the mechanism has not been fully elucidated. A new study shows that bacteria in the mouth, which produce nitrite, is key to the whole process. The use of mouthwash to reduce the number of these bacteria prevents the expected benefit of exercise on the blood pressure.
The drop in blood pressure following acute exercise, called post-exercise hypotension (PEH), is seen in both healthy people and hypertensives, and persists for a few hours. This is due to vasodilation, or the widening of blood vessels. One theory was that the increased synthesis of nitric oxide (NO) in endothelial cells with exercise. This is because of the increased production of endothelial nitric oxide synthase (eNOS), but other studies showed that inhibiting NOS failed to suppress PEH. However, this could be because NO can also be formed by another pathway that was not inhibited in this experiment.
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The current study was designed to test the possibility that nitrite formed in the mouth by oral bacteria is involved in PEH. The salivary glands absorb a quarter of nitrate in the circulation and excrete it into the mouth through saliva. Specific nitrate-reducing bacteria convert this to nitrite which is quickly absorbed into the blood stream. This is reduced to NO, which produces vasodilation. This causes more PEH as well as higher levels of oxygenation in the muscle tissues. Exercise also increases the production of NO from nitrate via an enzyme called xanthine oxidoreductase (XOR). These two pathways keep NO concentrations constant under a range of conditions occurring in the body.
Using mouthwash reduces the activity of this pathway, and some studies have shown that resting systolic blood pressure goes up after mouthwash is used for a few days. The current study aimed at showing how oral nitrate conversion by bacteria is linked to blood pressure regulation in humans. The key focus was on detecting exercise-stimulated increase in NO production, and the effect of antibacterial mouthwash on oral bacteria, weakening this response.
How was the study done?
22 participants were included. All participants were nonsmokers, had a BMI below 30, had no high blood pressure, high cholesterol levels, or diabetes. gingivitis or periodontitis, nor had they used mouthwash or tongue cleaners. Antibiotic use within the three months prior to the study start date was excluded. There were 15 males and 8 females, with an average age of 27 years. The average age was 72 kg and BMI was 23. The systolic and diastolic blood pressure (SBP and DBP) were similar before exercise in both groups.
Participants first did a treadmill test to find their maximal aerobic capacity. They also had blood tests, saliva tests, and blood pressure measurement done. Reactive hyperemia was also tested. Finally, on the next visit they did a treadmill workout, following which mouthwash vs placebo was provided. The blood pressure was measured again in the same way, with blood and saliva sampling before and after exercise. After one week, during a third visit, the same procedure was performed but the groups were crossed over to receive placebo where they used mouthwash before, and vice versa.
What did the study show?
After exercise and placebo use, the DBP fell by -2.4 mmHg on average, after one hour, but by only -1.7 mmHg after mouthwash use – a difference of almost 30%. After two hours following exercise and placebo, it fell by -0.9 mmHg, which was not significantly decreased from pre-exercise levels. However, with mouthwash use, the DBP rose significantly by 1.8 mmHg at 2 hours, even though the difference from the placebo group was not significant.
The SBP post-exercise fell by -5.2 mmHg with placebo but only -2.0 mmHg with mouthwash, a difference of 62%. It remained lower at -3.8 mmHg at 2 hours after placebo, a significant difference, but failed to respond at all after antibacterial mouthwash. Both readings thus showed significant differences between treatment groups.
The mean arterial pressure (MAP) also went down at one hour post-exercise in the placebo group but the response was 45% less following mouthwash use. At two hours the difference in the placebo group was still significant at -1.9 mmHg, but not with mouthwash use. However, the difference between the two groups was not significant. Reactive hyperemia tests showed increased tissue oxygenation was increased after exercise with placebo use but not after the mouthwash.
Again, plasma nitrite levels were increased by 40% after placebo but not after mouthwash use. The mouthwash also reduced salivary nitrite levels significantly, from 129 µM to 9 µM. at the same time salivary nitrate levels zoomed from about 250 µM to almost 650 µM for an increase of almost 160% On the other hand, the placebo group had a higher salivary nitrite but lower salivary nitrate levels than the mouthwash group.
The mouthwash did not produce any change in the relative proportions of the different bacteria present in the mouth within the two hours after administration. One bacterial species called Selenomonas was positively linked to plasma nitrite levels post-exercise, in the placebo group in each experiment.
What do we learn?
The use of antibacterial mouthwash significantly weakens the response of blood pressure and tissue oxygenation to exercise by inhibiting oral bacteria. This is linked to lower levels of nitrite in both saliva and plasma post-exercise. Thus the study shows for the first time that the presence of oral nitrate-reducing bacteria is important in normal exercise-induced changes in the cardiovascular system. The fact that the increase in plasma nitrite is seen at 2 hours after exercise without mouthwash use indicates the essential role of the oral bacteria in keeping nitrite levels constant to produce vasodilation in the post-exercise recovery period in healthy people.
Researcher Craig Cutler says, “These findings show that nitrite synthesis by oral bacteria is hugely important in kick-starting how our bodies react to exercise over the first period of recovery, promoting lower blood pressure and greater muscle oxygenation. If they are removed, nitrite can't be produced and the vessels remain in their current state.”
Exercise may also enhance the production of nitrate in the body or increase the salivary excretion of circulating nitrate, and more work is required to find out the source of the large nitrate increase seen post-exercise. While no acute change was observed in the oral microbiome, this does not preclude the existence of a more delayed alteration. Other studies by the same laboratory have shown a substantial variation by phylum, genus and species following a twice –weekly use of mouthwash by healthy people. Thus the acute and chronic effects of mouthwash may vary. Its use is linked to increased glucose and lactate in saliva, which may predispose to increased periodontal disease and therefore cardiovascular disease.
Finally, other studies have shown that there is a significant increase in SBP after using mouthwash for three and for seven days. More than $1.4 billion worth of mouthwashes are sold in the US, and the common incidence of hypertension could make this a matter of concern.
The study was published in the journal Free Radical Biology and Medicineon July 29, 2019.
Post-exercise hypotension and skeletal muscle oxygenation is regulated bynitrate-reducing activity of oral bacteria. C. Cutler, M. Kiernan, J.R. Willis, L. Gallardo-Alfaro, P. Casas-Agustench, D. White,M. Hickson, T. Gabaldon, & R. Bescos. Free Radical Biology and Medicine 143 (2019) 252–259. https://doi.org/10.1016/j.freeradbiomed.2019.07.035, https://www.sciencedirect.com/science/article/pii/S0891584919307610?via%3Dihub