Nitric oxide (NO) produced by endothelial cells plays a role in numerous processes in the body including vasodilation, platelet aggregation and leukocyte adhesion. The plasma concentration of NO, measured as the stable metabolites nitrate and nitrite - referred to as NOx, can be measured and used to indicate endothelial function. As in man with heart failure, mitral regurgitation (MR) associated with mitral valve prolapse in dogs, has been found to be associated with a decreased plasma concentation of NOx early in the course of heart failure. Correction of such endothelial dysfunction in human subjects is regarded as being an important therapeutic target.An aim of this PhD project is to investigate the involvement of NO in mitral valve disease and explain possible reasons for the decrease in NOx seen in connection with MR.When dogs are examined under clinic conditions there is an inevitable amount of stress and agitation, which may affect the cardiovascular system and endothelial function. Plasma NOx measured in dogs with MR in their home environment was similar to that of dogs without MR which were measured in the clinic. However, the same dogs with MR showed a significant decrease in plasma NOx when the sample was taken in the clinic (12.46±10.45 vs. 20.58±8.23 µM NOx for clinic vs. home samples, P = 0.02).Another study evaluated whether plasma NOx was influenced by an increased level of activity in normal dogs. This study showed a tendency towards a decrease in plasma NOx during the day, however, exercise significantly increased the plasma NOx (1.78±1.24 vs. 8.19±4.13 µM NOx before and after exercise, respectively, P < 0.001). A third study is currently under way to examine whether plasma NOx is affected by stress in dogs with and without MR. Samples for the measurement of plasma NOx are being taken both in the dogs' home and later the same day in the clinic. Four groups of dogs are included: two control breeds and a third breed comprising dogs with and without MR. The results and conclusions of this study will be presented at the Sandbjerg Meeting.