THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS FOSINOPRIL AND ENALAPRILDIFFER IN THEIR CENTRAL NERVOUS EFFECTS IN HUMANS

Background Although the antihypertensive actions of different angioten sin converting enzyme (ACE) inhibitors are comparable, they may affect central nervous activity, mood and well-being differently. Thus, cent ral nervous actions of ACE inhibitors may represent an essential facto r determining compliance with antihypertensive therapy. Objective To c ompare central nervous effects of the biochemically different ACE inhi bitors fosinopril and enalapril in healthy men. Methods In a double-bl ind cross-over study, auditory event-related brain potentials and hear t rate variability were assessed 6 h after oral intake of placebo, ena lapril (10 mg) and fosinopril (20 mg) with the doses being equipotent with regard to systemic ACE inhibition. Plasma concentrations of norad renaline, adrenaline, vasopressin and cortisol were determined 3 and 6 h after drug intake. Central nervous effects mediated via direct syst emic hypotensive actions were avoided (although not completely ruled o ut) by including only subjects (n = 14) who displayed no substantial d rop 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 si milar effect of fosinopril failed to reach significance, There was no clearcut 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 ena lapril on mechanisms regulating stimulus-induced cortical arousal and central nervous sympathetic outflow The effects diverging between enal april and fosinopril indicate that access to human brain functions dif fers among the various types of ACE inhibitors.