title: Clinical study with azelnidipine in patients with essential hypertension. Antiarteriosclerotic and cardiac hypertrophy-inhibitory effects and influence on autonomic nervous activity.
abstract: A dihydropyridine calcium (Ca) antagonist, azelnidipine (CAS 123524-52-7, Calblock), exhibits hypotensive effects for a prolonged duration, and has been reported to have a strong antiarteriosclerotic action due to its high affinity for vascular tissues and antioxidative action. It has also been reported that azelnidipine does not cause tachycardia associated with the baroreceptor reflex due to vasodilatation. In this study, the antiarteriosclerotic and cardiac hypertrophy-inhibitory effects, and the autonomic nervous activity in essential hypertension of azelnidipine were investigated. The study was performed using the following 2 protocols: 1) Pulse wave velocity (PWV), carotid arterial intima media thickness (IMT), echocardiography, high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), adiponectin, brain natriuretic peptide (BNP), and 8-isoprostane were measured after an initial treatment with azelnidipine. 2) The treatment was switched to azelnidipine in patients who had previously been under treatment with amlodipine for essential hypertension, and 123I-metaiodobenzylguanidine myocardial scintigraphy (123I-MIBG), measurements of plasma norepinephrine, atrial natriuretic peptide (ANP), and BNP, Holter electrocardiography, and heart rate variability analysis were performed. PWV, IMT, hs-CRP, IL-6, and TNF-alpha significantly decreased. The levels of 8-isoprostane, an antioxidative marker, were also significantly decreased, while adioponectin levels were significantly increased after the initial treatment with azelnidipine. After switching from amlodipine, azelnidipine exhibited a hypotensive effects comparable to amlodipine, and significantly decreased heart rate and the total number of extrasystoles. Noradrenaline levels and the LF/HF ratio were significantly decreased, and the washout rate was significantly reduced on 123I-MIBG myocardial scintigraphy. These findings suggest that azelnidipine inhibits the enhancement of sympathetic nervous activity and the progression of arteriosclerosis through its antioxidative effects.
authors.affiliation: Department of Digestive and Cardiovascular Medicine, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Teru
authors.initials: T
authors.lastname: Nada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nomura
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Koshiba
authors.forename: Tomohito
authors.initials: T
authors.lastname: Kawano
authors.forename: Jyunichi
authors.initials: J
authors.lastname: Mikawa
authors.forename: Susumu
authors.initials: S
authors.lastname: Ito
mesh_terms: D019797:3-Iodobenzylguanidine; D054392:Adipokines / Q000378:metabolism; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism; D001161:Arteriosclerosis / Q000150:complications / Q000000981:diagnostic imaging; D001341:Autonomic Nervous System / Q000187:drug effects; D001383:Azetidinecarboxylic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000209:etiology; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002395:Catecholamines / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004095:Dihydropyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D011674:Pulse; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals
chemical_list: D054392:Adipokines; D000959:Antihypertensive Agents; D000975:Antioxidants; D002121:Calcium Channel Blockers; D002395:Catecholamines; D016207:Cytokines; D004095:Dihydropyridines; D019275:Radiopharmaceuticals; D020097:Natriuretic Peptide, Brain; D019797:3-Iodobenzylguanidine; D001383:Azetidinecarboxylic Acid; C061679:azelnidipine