RESUMO
Native highlanders (e.g. Sherpa) demonstrate remarkable hypoxic tolerance, possibly secondary to higher levels of circulating nitric oxide (NO) and increased microcirculatory blood flow. As part of the Xtreme Alps study (a randomised placebo-controlled trial of dietary nitrate supplementation under field conditions of hypobaric hypoxia), we investigated whether dietary supplementation with nitrate could improve NO availability and microvascular blood flow in lowlanders. Plasma measurements of nitrate, nitrite and nitroso species were performed together with measurements of sublingual (sidestream dark-field camera) and forearm blood flow (venous occlusion plethysmography) in 28 healthy adult volunteers resident at 4559â¯m for 1 week; half receiving a beetroot-based high-nitrate supplement and half receiving an identically-tasting low nitrate 'placebo'. Dietary supplementation increased plasma nitrate concentrations 4-fold compared to the placebo group, both at sea level (SL; 19.2 vs 76.9⯵M) and at day 5 (D5) of high altitude (22.9 vs 84.3⯵M, pâ¯<â¯0.001). Dietary nitrate supplementation also significantly increased both plasma nitrite (0.78 vs. 0.86⯵M SL, 0.31 vs. 0.41⯵M D5, pâ¯=â¯0.03) and total nitroso product (11.3 vs. 19.7â¯nM SL, 9.7 vs. 12.3â¯nM D5, pâ¯<â¯0.001) levels both at sea level and at 4559â¯m. However, plasma nitrite concentrations were more than 50% lower at 4559â¯m compared to sea level in both treatment groups. Despite these significant changes, dietary nitrate supplementation had no effect on any measured read-outs of sublingual or forearm blood flow, even when environmental hypoxia was experimentally reversed using supplemental oxygen. In conclusion, dietary nitrate supplementation does not improve microcirculatory function at 4559â¯m.
Assuntos
Microcirculação/fisiologia , Nitratos/sangue , Adulto , Doença da Altitude/fisiopatologia , Velocidade do Fluxo Sanguíneo , Suplementos Nutricionais , Feminino , Humanos , Masculino , Nitratos/administração & dosagem , Nitratos/metabolismo , Nitritos/sangue , Compostos Nitrosos/sangue , Adulto JovemRESUMO
Nitric oxide (NO) production plays a central role in conferring tolerance to hypoxia. Tibetan highlanders, successful high-altitude dwellers for millennia, have higher circulating nitrate and exhaled NO (ENO) levels than native lowlanders. Since nitrate itself can reduce the oxygen cost of exercise in normoxia it may confer additional benefits at high altitude. Xtreme Alps was a double-blinded randomised placebo-controlled trial to investigate how dietary nitrate supplementation affects physiological responses to hypoxia in 28 healthy adult volunteers resident at 4559â¯m for 1 week; 14 receiving a beetroot-based high-nitrate supplement and 14 receiving a low-nitrate 'placebo' of matching appearance/taste. ENO, vital signs and acute mountain sickness (AMS) severity were recorded at sea level (SL) and daily at altitude. Moreover, standard spirometric values were recorded, and saliva and exhaled breath condensate (EBC) collected. There was no significant difference in resting cardiorespiratory variables, peripheral oxygen saturation or AMS score with nitrate supplementation at SL or altitude. Median ENO levels increased from 1.5/3.0â¯â¯mPa at SL, to 3.5/7.4â¯mPa after 5 days at altitude (D5) in the low and high-nitrate groups, respectively (pâ¯=â¯0.02). EBC nitrite also rose significantly with dietary nitrate (pâ¯=â¯0.004), 1.7-5.1â¯â¯µMâ¯at SL and 1.6-6.3⯵Mâ¯at D5, and this rise appeared to be associated with increased levels of ENO. However, no significant changes occurred to levels of EBC nitrate or nitrosation products (RXNO). Median salivary nitrite/nitrate concentrations increased from 56.5/786⯵M to 333/5,194â¯â¯µM⯠with nitrate supplementation at SL, and changed to 85.6/641⯵M and 341/4,553⯵M on D5. Salivary RXNO rose markedly with treatment at SL from 0.55⯵M to 5.70⯵M. At D5 placebo salivary RXNO had increased to 1.90⯵M whilst treatment RXNO decreased to 3.26⯵M. There was no association with changes in any observation variables or AMS score. In conclusion, dietary nitrate supplementation is well tolerated at altitude and significantly increases pulmonary NO availability and both salivary and EBC NO metabolite concentrations. Surprisingly, this is not associated with changes in hemodynamics, oxygen saturation or AMS development.