RAPID DECREASE IN SERUM ENDOTHELIN-1 LEVE LS AFTER TREATMENT WITH ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR IN CHRONIC CARDIAC-FAILURE

Circulating endothelin-1, a very strong peptide vasoconstrictor first discovered in 1988, is raised in cardiac failure. This increase contri butes to the deleterious effects of cardiac failure. Although specific anti-endothelin drugs are under development in this condition, the ef fects of more commonly used drugs on circulating endothelin-1 levels a re not well known. The aim of this study was to evaluate the effects o f ACE inhibitor therapy on plasma endothelin-1. levels in cardiac fail ure. The plasma endothelin-1 levels were measured in 24 patients (stag es III and IV of the NYHA classification), before and after treatment with angiotensin converting enzyme inhibitor (Captopril:test doses, th en 75 mg/day). A control group of 10 paired patients was used to shake off the effects of bed rest and hospital salt-free diet. The initial endothelin-1 levels were high but equivalent in the control and study groups: 9.13 +/- 1.87 fmol/mL vs 8.98 +/- 1.92 fmol/ml. Plasma endothe lin-1 decreased significantly in the study group 72 hours after beginn ing ACE inhibitor therapy (7.44 +/- 1.95, p < 0.02) but remained highe r than normal (p < 0.01), whereas the values in the control group rema ined the same. This study demonstrates a decreases in plasma endotheli n-1 levels 72 hours after onset of ACE inhibitor therapy in patients w ith stable severe cardiac failure. This result, already suggested by m any experimental studies and certain ancillary clinical trials, could explain some of the beneficial effects of ACE inhibitors in this condi tion.