The angiotensin converting enzyme inhibitors fosinopril and enalapril differ in their central nervous effects in humans

Background. Although the antihypertensive actions of different angiotensin converting enzyme (ACE) inhibitors are comparable, they may affect central nervous activity, mood and well-being differently. Thus, central nervous actions of ACE inhibitors may represent an essential factor determining compliance with antihypertensive therapy, Objective. To compare central nervous effects of the biochemically different ACE inhibitors fosinopril and enalapril in healthy men. Methods. In a double-blind cross-over study, auditory event-related brain potentials and heart rate variability were assessed 6 h after oral intake of placebo, enalapril (10 mg) and fosinopril (20 mg) with the doses being equipotent with regard to systemic ACE inhibition. Plasma concentrations of noradrenaline, adrenaline, vasopressin and cortisol were determined 3 and 6 h after drug intake, Central nervous effects mediated via direct systemic hypotensive actions were avoided (although not completely ruled out) by including only subjects (n = 14) who displayed no substantial drop in blood pressure following intake of the ACE inhibitors. Results Enalapril, but not fosinopril, enhanced the N1 component and the N1-P2 amplitude of the event-related brain potential (P < 0.05). In addition, enalapril enhanced plasma noradrenaline concentrations (P < 0.05). A similar effect of fosinopril failed to reach significance. There was no clear-cut effect of ACE inhibition on heart rate variability, and also plasma concentrations of adrenaline, vasopressin and cortisol remained unaffected. Conclusion. The results suggest an enhancing effect of enalapril on mechanisms regulating stimulus-induced cortical arousal and central nervous sympathetic outflow The effects diverging between enalapril and fosinopril indicate that access to human brain functions differs among the various types of ACE inhibitors.