Changes in pulmonary vascular function after acute methionine loading in normal men

Elevated blood levels of Hcy (homocysteine) are associated with endothelial dysfunction in the systemic and coronary arterial beds. We wished to know if similar changes could be detected in the pulmonary circulation, using non-invasive tests. We studied ten normal young men aged 23–31 years, in whom acute hyperhomocysteinaemia was induced by oral ingestion of methionine. Cardiopulmonary exercise testing [including measurement of exhaled breath NO (nitric oxide)] was performed on two occasions, with and without methionine loading. In addition, blood samples for vWf (von Willebrand factor) and factor VIIIc were taken as markers of endothelial function. After oral methionine, plasma Hcy increased from 11.8±3.1 to 31.2±10.3 µmol/l (values are means±S.D.; P<0.0001), whereas there was no increase after placebo. After exercise there was an increase in VNO (NO production) and circulating plasma levels of vWf and factor VIIIc, but these were similar in the two tests. Exercise time, HR (heart rate) and BP (blood pressure) responses and PVO₂ (peak achieved O₂ uptake) were also similar in the two tests. V_E (expiratory minute ventilation)/VCO₂ (CO₂ production) was similar in the two groups at rest (methionine, 31.9±3.9; placebo, 30.5±3.9; P=0.11), but increased during exercise after methionine (at peak, 32.2±4.6 compared with 29.9±2.8; P=0.016). PETCO₂ (end-tidal partial pressure of CO₂) was also similar in the two groups at rest (35.1±2.9 compared with 36.8±3.2; P=0.11), but decreased throughout the methionine test (peak 34.1±4.4 compared with 36.7±3.5; P=0.006). V_E vs VCO₂ slope also increased in the methionine test (25.2±2.4 compared with 22.8±2.3; P=0.003). In conclusion, small, but consistent and significant, changes in respiratory gas exchange were seen after methionine loading, compatible with a V/Q (ventilation/perfusion) mismatch due to pulmonary vascular endothelial dysfunction.