EXERCISE INCREASES ENDOTHELIN-1 PLASMA-CONCENTRATIONS IN PATIENTS WITH CORONARY-ARTERY DISEASE - MODULATORY ROLE OF LDL CHOLESTEROL AND OF PENTAERITHRITYLTETRANITRATE

Previous studies suggest that ET-1 plays a role in induction of coronary artery disease (CAD). It was shown that secretion of endothelin-1 (ET-1) by the vascular endothelium is enhanced in atherosclerotic alterations and may be antagonized by EDRF. The objective of the present study was to investigate the effects of ergometric exercise on plasma ET-1 concentrations, and the potential modulatory role of LDL cholesterol, and the effects of an orally administered nitrate, PETN, in patients with CAD. Ten men with CAD and 10 healthy men underwent bicycle ergometry according to the WHO-standards. Venous blood samples for determination of ET-1 concentrations were drawn directly before and 5 min after ergometric exercise. Patients were randomized and treated for 72 h in a crossover design either with placebo or pentaerithrityltetranitrate (PETN). After 72 h the identical ergometric protocol was repeated. Basal plasma levels of ET-1 were 6.1 +/- 0.7 pg/ml (patients) and 5.5 +/- 0.6 pg/ml (controls) (n.s.). After ergometric exercise ET-1 plasma concentrations rose significantly (7.3 +/- 0.9 pg/ml; p < 0.05) in the patient group under placebo treatment, whereas they remained constant (5.5 +/- 0.7 pg/ml) with PETN treatment. ET-1 levels remained unaffected by ergometric exercise in healthy controls. Mean LDL cholesterol plasma levels in patients with CAD were 156 +/- 8 mg% and 152 +/- 7 mg% in healthy controls. In the patient group there was a significant (p < 0.002) positive correlation between the exercise-induced increase in ET-1 and the LDL cholesterol plasma concentrations (r = 0.85). Blood pressure and heart rate were not modified by PETN treatment. In patients with CAD bicycle ergometry induced an increase in ET-1 plasma concentrations. The positive correlation with the LDL cholesterol plasma levels indicates that LDL cholesterol is involved in regulation of ET-1 secretion in vivo. PETN therapy completely abolished the exercise-induced increase in ET-1 plasma levels. This may result from local hemodynamic effects of the nitrate; hypothetically a nitrate-induced rise in the local NO concentrations can be considered. The clinical implications of these findings remain elusive. However, the findings of the present study are in accordance with the beneficial clinical effects of nitrates in patients with CAD.