Effect of Nitrite on Exercise Physiology and Metabolism

This study will examine how nitrite infusions affect exercise tolerance (how much a person can exercise before having to stop). Exercise ability is limited by how fast oxygen can be delivered to the body and how fast the body can produce energy. Both of these processes are affected by nitric oxide (NO), a gas produced by cells that line blood vessels. NO is important in regulating blood vessel dilation, and consequently, blood flow. Nitrite may act as a storehouse for nitric oxide and be able to improve exercise tolerance. Healthy normal volunteers between 21 and 45 years of age who can use an exercise bicycle may be eligible for this study. Candidates are screened with a medical history, physical examination, electrocardiogram, breathing tests, blood tests, and a pregnancy test for women who are able to bear children. Pregnant women are excluded from the study. The screening session includes practice exercise on the bicycle. Participants exercise on a stationery exercise bicycle for about 30 minutes on each of two study days. During the test, they breathe in and out of a mouthpiece that allows inhaled and exhaled respiratory gases to be measured. Before subjects begin to exercise, a small tube is placed in the artery of their forearm inside the elbow. A longer tube called a central line is placed in a deeper vein in the neck after the area has been numbed. A thinner tube, called a pulmonary artery catheter, is placed through the central line and advanced into the chambers of the heart, through the heart valve, and into the lung artery. This catheter measures various pressures directly in the heart and lungs. Blood samples are drawn through the catheter also, to avoid the need for multiple needle sticks. Another tube is placed in the vein of the other arm to deliver medications. Thirty minutes after all the tubes are placed, a blood sample is drawn for baseline measurements. Then, either saline (sterile salt water) or nitrite is injected into the tube in the arm