The lining of blood vessels (endothelium) releases substances that cause relaxation of smooth muscle that underlies the lining. The relaxation of the smooth muscle is essential in maintaining normal blood vessel tone and thus the control of blood flow. Deficiency in the release of nitric oxide would lead to inappropriate dilation of blood vessels and thus to limitation of the blood flow increase. To examine whether the relaxation of blood vessels that accompanies periods when the heart rate increases, we studied the effect of L-NMMA, which is an inhibitor of release of nitric oxide, on the blood flow increase produced by rapidly pacing the heart. Normally, pacing the heart produces a 33% increase in blood flow, but this was reduced to 9% after blocking the release of nitric oxide with L-NMMA. This suggests that release of nitric oxide from the lining of blood vessels in the heart is important in relaxing arteries and thus controlling blood flow in the heart. Conditions that lead to abnormalities of the function of the lining of the heart could, by reducing blood flow, lead to worsening of angina.