Abstract Aim: The purpose of the study is to show the influence of Proton Pump Inhibitors (PPI in form of esomeprazole) on the bioactivation of dietary nitrate (sodium-nitrate solution) in submaximal exercise, through affecting the gastric pH. Method: Randomized, doubled-blinded, placebo-controlled and crossover study with six subjects (mean ± SD, age 29 ± 5years, height 170 ± 5 centimeters, weight 70 ± 5 Kg, BMI 24,36 ± 1,75 Kg/m2 blood pressure 119/ 77 ± 6 mmHg, 3 male and 3 female). They were tested in two different trials. Every trial consisted of two parts. One part was cycling on 4 different submaximal stages (80W/60RPM, 80W/90RPM, 120W/60RPM, 120W/90RPM) for 5 minutes each, with 90 minutes rest in between. The same protocol was repeated. In the beginning of the resting time a sodium nitrate solution (NaNO3-, 10mg/kg body weight) was ingested. VO2, VCO2, RER, VE, Lactate, Glucose, heart rate and blood pressure were recorded. Venous blood samples were taken. Whether esomeprazole (10mg) or a placebo were taken 24h, 12h and directly before being tested in both trials. Subjects were pleased to have a nitrate poor diet starting when taking the pills. An information sheet was provided. Results: No significant differences were found between the post values and the treatment. Tendencies of a higher oxygen consumption when taking esomeprazole (2,62%) in comparison to placebo (0,11%) were observed. Systolic BP decreased by 3,91% with the placebo while it decreased just 2,04% with esomeprazole after intake. Sex-specific differences occurred in the metabolism of esomeprazole and dietary nitrate. RER showed a significant post nitrate difference between the female and male participants with t=.006 and a significance in predietary nitrate intake. VE in female (40,79 ± 7,20 L/min) and (50,03 ± 10,09 L/min) in male were as well significant (t=.017). Conclusion: Tendencies of effects of PPI are seen in the post-values of VO2 and BP after intake of dietary nitrate. Gender-differences are shown in RER and VE. More research is needed to see the impact of dietary nitrate on the human body under submaximal load.

The rising number of the population that present with major depressive disorder has intensified the need to identify and elucidate new biological markers for the diagnosis and treatment of depression. Depression presents with evidence of changes in the nitric oxide (NO) pathway. In this study, levels of various endogenous markers of the NO cascade, viz. nitrite (NO2–), asymmetrical dimethylarginine (ADMA) and arginase II activity, were investigated in the Flinders Sensitive Line (FSL) rat, a genetic animal model of depression. The aim of the current study was to determine if there are differences between these markers in the plasma of the FSL rat compared to its healthy control, the (Flinders Resistant Line) FRL rat, with the possibility of considering their use as biomarkers of depression. Nitrite was chosen as metabolite over nitrate (NO3–) because the dietary intake of nitrite and/or nitrate does not significantly affect nitrite (NO2–) levels in plasma. Although this is of no significance if applied to rats, it is an important factor to be considered when doing clinical studies. For neurochemical determination of nitrite a sensitive fluorometric reversed phase high–performance liquid chromatographic (HPLC) assay was developed to analyze nitrite in human and rat plasma. Derivatization of sample nitrite was performed with 2,3–diaminonaphthalene (DAN) followed by the quantification of the stable and highly fluorescent product, 2,3–naphthotriazole (NAT). Determination of arginase II activity was performed by measuring L–arginine and L–ornithine concentrations in the plasma, while ADMA was measured simultaneously with L–arginine and L–ornithine using liquid chromatography/tandem mass spectrometry, or LC/MS/MS. Plasma nitrite levels of FSL rats were significantly decreased compared to plasma nitrite levels in the FRL rat, but neither the levels of ADMA nor arginase II activity showed a significant difference between the FSL and FRL rat groups. From these results it is concluded that in accordance with previous studies, the NO pathway plays an important role in the pathophysiology of depression, as depicted in the differences found between plasma nitrite levels in the FSL rat compared to its healthy control. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2011.

The rising number of the population that present with major depressive disorder has intensified the need to identify and elucidate new biological markers for the diagnosis and treatment of depression. Depression presents with evidence of changes in the nitric oxide (NO) pathway. In this study, levels of various endogenous markers of the NO cascade, viz. nitrite (NO2–), asymmetrical dimethylarginine (ADMA) and arginase II activity, were investigated in the Flinders Sensitive Line (FSL) rat, a genetic animal model of depression. The aim of the current study was to determine if there are differences between these markers in the plasma of the FSL rat compared to its healthy control, the (Flinders Resistant Line) FRL rat, with the possibility of considering their use as biomarkers of depression. Nitrite was chosen as metabolite over nitrate (NO3–) because the dietary intake of nitrite and/or nitrate does not significantly affect nitrite (NO2–) levels in plasma. Although this is of no significance if applied to rats, it is an important factor to be considered when doing clinical studies. For neurochemical determination of nitrite a sensitive fluorometric reversed phase high–performance liquid chromatographic (HPLC) assay was developed to analyze nitrite in human and rat plasma. Derivatization of sample nitrite was performed with 2,3–diaminonaphthalene (DAN) followed by the quantification of the stable and highly fluorescent product, 2,3–naphthotriazole (NAT). Determination of arginase II activity was performed by measuring L–arginine and L–ornithine concentrations in the plasma, while ADMA was measured simultaneously with L–arginine and L–ornithine using liquid chromatography/tandem mass spectrometry, or LC/MS/MS. Plasma nitrite levels of FSL rats were significantly decreased compared to plasma nitrite levels in the FRL rat, but neither the levels of ADMA nor arginase II activity showed a significant difference between the FSL and FRL rat groups. From these results it is concluded that in accordance with previous studies, the NO pathway plays an important role in the pathophysiology of depression, as depicted in the differences found between plasma nitrite levels in the FSL rat compared to its healthy control. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2011.