Differential effects of enalapril–felodipine versus enalapril–lercanidipine combination drug treatment on sympathetic nerve traffic and metabolic profile in obesity-related hypertension

• The neurometabolic effects of two ACEI/calcium blockers combination were examined.
• Enalapril/lercanidipine caused a lesser sympathoexcitation than enalapril/felodipine.
• Insulin sensitivity improved only during enalapril/lercanidipine treatment.

Scanty information is available on the effects of combination drug treatment based on an ACE inhibitor and a calcium channel blocker on the neurometabolic alterations characterizing obesity-related hypertension (OHT). After 2-week run-in with enalapril (20 mg), 36 OHTs were randomized according to a double-blind crossover design to a combination therapy with either lercanidipine 10 mg (L) or felodipine extended release 5 mg (F), each lasting 8 weeks. Measurements included clinic and ambulatory blood pressure (BP) and heart rate, homeostasis model assessment index, plasma norepinephrine, and muscle sympathetic nerve activity. Patients with uncontrolled BP were then uptitrated to 20 mg/d (L) and 10 mg/d (F) combined with enalapril 20 mg, respectively, for further 8 weeks. For similar BP reductions, enalapril–lercanidipine (EL) caused norepinephrine and MSNA increases significantly less pronounced than those seen with enalapril–felodipine, the lesser sympathoexcitation observed with EL being coupled with a significant improvement in homeostasis model assessment index. This was the case also when L and F were uptitrated in the combination. In OHT, at variance from enalapril–felodipine, EL combination is almost entirely devoid of any major sympathoexcitatory effect and is associated with an improvement in insulin sensitivity.