Influence of intensive physical training on urinary nitrate elimination and plasma endothelin-1 levels in patients with congestive heart failure

Background. Congestive heart failure (CHF) is associated with increased peripheral vascular resistance. Exercise-induced shear stress may release endothelial relaxing factors, such as nitric oxide (NO), and inhibit the production of vasoconstrictors such as endothelin-1 (ET-1) thereby modulating vascular tone. We examined the effect of intensive training on ET-1 plasma concentrations and NO-metabolite elimination in patients with CHF after acute myocardial infarction. Methods. Seventeen patients with CHF after a myocardial infarction were randomized to an exercise group (n = 9), who performed physical training for 8 weeks, or a control group (n = 8) who received usual care. A physical examination, pulmonary function test, and a maximum exercise test were performed, and 24-hour urinary nitrate elimination and ET-1 in plasma were determined before and at the end of the study period. Results. Maximal oxygen uptake remained unchanged in controls (17.9 ± 1.4 to 18.1 ± 1.5 mL/(kg min) but increased in the exercise group (from 20.4 ± 0.75 to 26.7 ± 1.4 mL/(kg min). After 8 weeks the urinary nitrate elimination in controls was significantly decreased (1.25 ± 0.20 to 1.03 ± 0.22 mmol/24 hours; P < 0.001), while it was unchanged in the exercise group (1.26 ± 0.23 to 1.39 ± 0.28; P = 0.71). Plasma ET-1 levels did not change after 8 weeks (7.87 ± 0.62 versus 7.57 ± 0.75 and 7.13 ± 0.6 versus 7.35 ± 0.7 pg/mL for control and exercise groups, respectively). Conclusion. In patients with CHF after acute myocardial infarction nitrate elimination decreases over the subsequent 2 months. This trend was reversed by training. Because nitrate elimination mirrors endogenous NO production, these results suggest that training may positively influence endothelial vasodilator function.