Effects of nitrite on long-term peripheral chemoreflex in healthy and high fat diet-fed rats

Abstract

Inorganic nitrate and nitrite supplementation improves endothelial function, decreases blood pressure, increases ejection fraction, and decreases overall weight. It also attenuates the hypoxic ventilatory response (HVR) in healthy humans. The HVR is increased in obese humans when compared to healthy individuals. Therefore, we hypothesize that HVR increases in a rat model of obesity and this increase is blunted by nitrite supplementation. First, we tested the hypothesis that nitrite supplementation decreases HVR in healthy, adult rats. Twelve, two-month-old, Fischer-344 rats were broken into two groups: rats fed a standard diet with additional nitrite supplementation (Nitrite) and rats fed a standard diet with no additional supplementation. After two months of nitrite supplementation, plethysmography and gas analysis was used to measure ventilation and metabolism at 21%, 15%, 12%, and 9% oxygen. In the second experiment, Twenty-one, seven-month-old, Fischer-344 rats were divided into three groups: rats fed a high fat diet (HFD), rats fed a high fat diet with additional nitrite supplementation in their drinking water (HFD+Nitrite), and rats fed a standard diet (Control). After 14 months of diet and nitrite supplementation, all three groups underwent plethysmography as in experiment 1. In the first experiment, nitrite supplementation significantly reduced HVR. In the longterm nitrite supplementation cohort, contrary to data in humans, the HVR was reduced in obese rats compared to control, nitrite did not alter this obesity-induced decrease in HVR. Nitrite did cause a significant increase in rate of oxygen consumption (V O2) when compared to both HFD rats and control rats. Future studies are needed to determine the mechanisms behind the impact of these interventions on HVR.