We have previously demonstrated a positive association between metabolic risk factors associated with impaired vascular reactivity and change in diastolic blood pressure (DBP) during exercise (Brett et al., 2000). An increase in DBP may result from impaired relaxation of resistance vasculature in skeletal muscle during exercise.

The aim of this study was to determine whether an acute elevation of homocysteine produced by methionine loading influences exercise DBP.

Healthy volunteers (18-62 years) participated in two randomised double blind cross over studies receiving methionine on one occasion and placebo on another occasion separated by at least 5 days. Studies were approved by the local research ethics committee and volunteers gave written informed consent. In study 1 (n=32), subjects received methionine 100mg/kg or placebo 4 hours before exercise and, in study 2 (n=11), methionine 100mg/kg 20 hours and 12 hours before exercise on one occasion and placebo at the same time points on the other occasion. BP was measured by a single trained observer using mercury sphygmomanometry at rest and during fixed low work load bicycle ergometry (3 mins at 50, 75 and 100 Watts).

All values are mean±SEM. Plasma total homocysteine increased following methionine (from 7.1±0.3 µmol/L to 22.5±1.2 µmol/L after a single dose of methionine, P<0.0001) but remained unchanged after placebo (6.9±0.4 µmol/L vs 7.1±0.4 µmol/L, P=NS). In both studies, resting values of systolic BP (SBP) and DBP following methionine were not significantly different from those following placebo (study 1: 122±2.3/73±1.7 vs 121±1.9/75±1.3 after methionine and placebo respectively; study 2: 124±4.1/78±3.1 vs 120±3.3/80±2.4, means±SEM, P=NS) The change, from resting values, in SBP during exercise was also similar following methionine and placebo. In study 1, SBP changed (relative to placebo) by -1.1±1.7, -2.6±2.5 and 0.3±2.5 mmHg at 50, 75 and 100 W respectively (P=NS by ANOVA for all workloads). In study 2, SBP changed by -0.4±2.5, 2.5±2.4 and -1.8±3.3 mmHg at 50, 75 and 100 W (P=NS). By contrast the change, from resting values, in DBP during exercise following methionine was significantly greater than that following placebo. In study 1, DBP 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=0.002 by ANOVA for all workloads). In study 2, DBP increased by 4.9±1.0, 5.4±2.1 and 6.1±1.1 mmHg at 50, 75 and 100 W respectively (P=0.0005).

An acute elevation of plasma homocysteine by methionine loading is associated with an increase in exercise DBP during low work load exercise. This finding supports the hypothesis that metabolic factors associated with impaired vascular reactivity have a greater influence on exercise rather than resting.

BP.Brett S.E. et al. 2000, Circulation, 101: 611-615.