title: Differential effects of enalapril-felodipine versus enalapril-lercanidipine combination drug treatment on sympathetic nerve traffic and metabolic profile in obesity-related hypertension.
abstract: 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.
authors.affiliation: Istituto Auxologico Italiano IRCCS, Milano, Italy.
authors.forename: Gino
authors.initials: G
authors.lastname: Seravalle
authors.affiliation: Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Brambilla
authors.affiliation: Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
authors.forename: Daniela Prata
authors.initials: DP
authors.lastname: Pizzalla
authors.affiliation: Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Casati
authors.affiliation: Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Riva
authors.affiliation: Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Cuspidi
authors.affiliation: Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Bombelli
authors.affiliation: Istituto Auxologico Italiano IRCCS, Milano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancia
authors.affiliation: Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy; IRCCS Multimedica, Sesto San Giovanni, Milano, Italy. Electronic address: guido.grassi@unimib.it.
authors.forename: Guido
authors.initials: G
authors.lastname: Grassi
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018660:Blood Pressure Monitoring, Ambulatory; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004095:Dihydropyridines / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000627:therapeutic use; D015736:Felodipine / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D007333:Insulin Resistance; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D009765:Obesity / Q000150:complications*; D011897:Random Allocation; D013564:Sympathetic Nervous System / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004656:Enalapril; D015736:Felodipine; C060343:lercanidipine; D009638:Norepinephrine
keywords: Combination drug treatment; lercanidipine; obesity-related hypertension; sympathetic activity