Are inhibitors of angiotensin converting enzyme able to control effectively activity of renin-angiotensin system during long term treatment of chronic heart failure?

Two consecutive open uncontrolled studies were conducted on patients with heart failure (NYHA class II-IV) due to ischemic heart disease or dilated cardiomyopathy. In study 1 activity of components of the renin-angiotensin-aldosterone system was determined in 44 patients after 2, 8, and 52 weeks of treatment with captopril. In study 2 activity of renin-angiotensin-aldosterone system, blood levels of atrial natriuretic factor and norepinephrine were determined in 54 patients before and at peak exercise on veloergometer prior to and after 3 months of treatment with enalapril (15,4+/-0,12 mg/day) given as adjunct to cardiac glycosides and diuretics. Results. Study 1. Despite stable inhibition of angiotensin converting enzyme and pronounced decrease of angiotensin II concentration in plasma effect of captopril on plasma level of aldosterone was incomplete and unstable. Significant decrease of aldosterone level (-40,4%; p<0,01) observed by the end of 2 weeks became less pronounced after 8 weeks. There was no significant difference between initial and 1 year plasma aldosterone levels (281,2+/-28,2 and 237,5+/-25,6 pg/ml, respectively, p=n.s.). Study 2. Enalapril caused insufficient inhibition of renin-angiotensin-aldosterone and sympathoadrenal systems since after treatment physical effort led to pronounced activation of these systems: increments of angiotensin II and aldosterone concentrations at peak exercise were 63 and 37%, 48 and 38% before and after enalapril, respectively Reactions of other neurohormones to exercise were also not altered by enalapril. Thus inhibitors of angiotensin converting enzyme were not able to attain complete control over activity of renin-angiotensin-aldosterone and sympathoadrenal systems.