Physiological role for nitrate-reducing oral bacteria in blood pressure control

Abstract

Circulating nitrate (NO ₃ ⁻), derived from dietary sources or endogenous nitric oxide production, is extracted from blood by the salivary glands, accumulates in saliva, and is then reduced to nitrite (NO ₂ ⁻) by the oral microflora. This process has historically been viewed as harmful, because nitrite can promote formation of potentially carcinogenic N-nitrosamines. More recent research, however, suggests that nitrite can also serve as a precursor for systemic generation of vasodilatory nitric oxide, and exogenous administration of nitrate reduces blood pressure in humans. However, whether oral nitrate-reducing bacteria participate in “setting” blood pressure is unknown. We investigated whether suppression of the oral microflora affects systemic nitrite levels and hence blood pressure in healthy individuals. We measured blood pressure (clinic, home, and 24-h ambulatory) in 19 healthy volunteers during an initial 7-day control period followed by a 7-day treatment period with a chlorhexidine-based antiseptic mouthwash. Oral nitrate-reducing capacity and nitrite levels were measured after each study period. Antiseptic mouthwash treatment reduced oral nitrite production by 90% ( p < 0.001) and plasma nitrite levels by 25% ( p = 0.001) compared to the control period. Systolic and diastolic blood pressure increased by 2–3 .5 mm Hg, increases correlated to a decrease in circulating nitrite concentrations ( r ² = 0.56, p = 0.002). The blood pressure effect appeared within 1 day of disruption of the oral microflora and was sustained during the 7-day mouthwash intervention. These results suggest that the recycling of endogenous nitrate by oral bacteria plays an important role in determination of plasma nitrite levels and thereby in the physiological control of blood pressure.

Highlights

► Antiseptic mouthwash use abrogates oral bacterial conversion of nitrate to nitrite. ► Interruption of the enterosalivary circulation reduces plasma nitrite levels. ► The reduction in plasma nitrite levels is associated with elevations in blood pressure. ► The results indicate the importance of oral nitrate-reducing bacteria in blood pressure control. ► Our findings intimate adverse effects of mouthwash by disturbing NO/nitrite homeostasis.