Elevation of plasma homocysteine by methionine loading increases the diastolic blood pressure response to exercise

Objective Exercise blood pressure is elevated in conditions associated with endothelial dysfunction. To determine whether this is a causal association, we examined the effects of endothelial dysfunction induced by methionine loading, on exercise blood pressure. Design Healthy subjects (18-63 years) participated in randomized, double-blind, cross-over studies receiving methionine and placebo on separate occasions before exercise. Methods In study 1 (n = 32), subjects received placebo and methionine 100 mg/ kg 4 h before exercise and, in study 2 (n = 11), placebo and methionine 200 mg/ kg (given as 100 mg 20 and 12 h before exercise). A further study confirmed that methionine 100 mg/ kg impaired brachial artery flow-mediated dilation. Blood pressure was measured by mercury sphygmomanometry at rest and during low workload bicycle ergometry. Results Plasma homocysteine increased after methionine compared to placebo (22.5 +/- 1.2 versus 7.7 +/- 0.7 mu mol/l in study 1, and 50.2 +/- 7.6 versus 12.8 +/- 1 0.7 mu mol/l in study 2, means +/- SE, each P < 0.0001). In both studies resting systolic and diastolic blood pressures and the increases in systolic blood pressure during exercise were similar after methionine and placebo. By contrast, exercise diastolic blood pressure responses (measured as the change from resting values) increased more after methionine than after placebo. In study 1, diastolic blood pressure responses increased relative to placebo by 3.5 +/- 1.0, 3.7 +/- 1.0 and 2.4 +/- 1.0 mmHg at 50, 75 and 100 W, respectively (P < 0.01). In study 2, diastolic blood pressure responses increased by 4.9 +/- 1.0, 5.4 +/- 2.1 and 6.1 +/- 1.1 mmHg at 50, 75 and 100 W, respectively (P < 0.001). Conclusion Endothelial dysfunction produced by methionine loading is associated with an increased exercise diastolic blood pressure response.