Effect of Nitrite on Exercise Physiology and Metabolism
کلید واژه ها
خلاصه
شرح
During exercise, there is a lag in the rate at which oxygen uptake (VO2) rises to meet energy demand. It is uncertain whether this limitation is due to inadequate O2 delivery to working muscle, limitations to the rate at which mitochondria can generate ATP to meet demand, or by a combination of both. Both of these limitations may be modulated by nitric oxide. Nitric oxide (NO) has been implicated in numerous physiological functions, including control of skeletal muscle vasodilation and oxidative metabolism. During exercise, NO will both vasodilate skeletal muscle and modulate (inhibit) mitochondrial respiration. The latter effect could either decrease oxygen extraction by limiting the ability of mitochondria to utilize oxygen, or paradoxically increase oxygen utilization by inhibiting mitochondria proximal to blood vessels, an effect that facilitates oxygen diffusion to distal tissue and mitochondria (NO dependent facilitated oxygen diffusion). Previous studies have demonstrated that NO production increases during exercise and regional inhibition of NO production from endothelial NO synthase reduces exercise-dependent blood flow by approximately 10%. NOS inhibitors such as N(G) -nitro-L-arginine methyl ester (L-NAME) have been shown to decrease exercise tolerance, and NO precursors (L-arginine) to increase exercise tolerance. Administration of inhaled NO during exercise has not been shown to increase exercise tolerance.
Considering the potential role of nitrite bioconversion to NO during hypoxia, is likely that nitrite plays an important role in modulating exercise physiology. We therefore hypothesize that during aerobic, and in particular anaerobic exercise, erythrocyte and plasma nitrite will be converted to NO and modulate muscle blood flow, mitochondrial respiration, oxygen diffusion and ultimately maximal oxygen consumption. While we expect these effects will increase maximal oxygen consumption and increase work output, it is also distinctly possible that NO production from nitrite during exercise will inhibit mitochondrial respiration and decrease maximal oxygen consumption. The purpose of the present study is to investigate the effects of aerobic-to-anaerobic exercise on circulating nitrite stores in erythrocytes and plasma in the arterial and central venous circulation and the effects of systemic nitrite infusion on aerobic and anaerobic exercise capacity. Physiological parameters including maximal oxygen consumption (VO2max), maximal CO2 and NO production (VCO2max and VNOmax), maximal work, rate of perceived exertion (RPE), anaerobic threshold, and pulmonary gas exchange (VO2, VCO2, VE) will be monitored during exercise with and without nitrite infusions. Our primary endpoint will be VO2 max with nitrite infusion compared to VO2 max with saline placebo infusion.
تاریخ
آخرین تأیید شده: | 08/15/2013 |
اولین ارسال: | 03/08/2005 |
ثبت نام تخمینی ارسال شد: | 03/08/2005 |
اولین ارسال: | 03/09/2005 |
آخرین بروزرسانی ارسال شده: | 07/02/2018 |
آخرین به روزرسانی ارسال شده: | 07/04/2018 |
تاریخ شروع مطالعه واقعی: | 03/07/2005 |
تاریخ تخمین اولیه اولیه: | 08/15/2013 |
تاریخ برآورد مطالعه: | 08/15/2013 |
شرایط یا بیماری
مداخله / درمان
Drug: Sodium Nitrite
فاز
معیارهای صلاحیت
سنین واجد شرایط تحصیل | 21 Years به 21 Years |
جنسیت واجد شرایط مطالعه | All |
داوطلبان سالم را می پذیرد | آره |
شاخص | - INCLUSION CRITERIA: Subjects must be 21-45 years of age. Subject must be in good health and able to perform cycle ergometry for the length of the study. Subjects must provide informed, written consent for participation in this study. Female subjects of childbearing age must have a negative pregnancy test. EXCLUSION CRITERIA: Subjects with a history of cardiac, pulmonary, peripheral vascular, or mitochondrial disease. Subjects with abnormal EKG other than sinus bradycardia. Individuals with a future cardiovascular risk greater than 1 % in the next 10 years will be excluded from the study. Risk will be calculated using the Framingham risk calculator published on the web site: http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof. Subjects with any physical condition (for example, knee problems) that may impair their performance during exercise testing. Subjects who have a history of smoking within one year. Subjects with anemia (defined as hemoglobin less than 10 g/dL). Subjects with a history of reaction to a medication or other substance characterized by dyspnea and cyanosis will not participate in this study. Subjects with G6PD deficiency. Subjects with a baseline methemoglobin level greater than 1%. Lactating females who are breastfeeding, will not participate since nitrite crosses into breast milk and could cause methemoglobinemia in the infant. No volunteer subject will be allowed to take any medication (oral contraceptive agents are allowed), vitamin supplements, herbal preparations, nutriceuticals or other alternative therapies for at least one month prior to study and will not be allowed to take aspirin or NSAIDs for one week prior to study. Subjects with a blood pressure of less than 100/70 mmHg on the study day will be excluded from the protocol. |