Arzneimittelforschung, Table of Contents

Arzneimittelforschung 2007; 57(11): 698-704
DOI: 10.1055/s-0031-1296670

Antihypertensives

Editio Cantor Verlag Aulendorf (Germany)

Clinical Study with Azelnidipine in Patients with Essential Hypertension

Antiarteriosclerotic and cardiac hypertrophy-inhibitory effects and influence on autonomic nervous activity

Teru Nada

¹Department of Digestive and Cardiovascular Medicine, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan

,

Masahiro Nomura

²Department of Human and Social Sciences, Faculty of Integrated Art and Sciences, University of Tokushima Graduate School, Tokushima, Japan

,

Kunihiko Koshiba

¹Department of Digestive and Cardiovascular Medicine, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan

,

Tomohito Kawano

¹Department of Digestive and Cardiovascular Medicine, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan

,

Jyunichi Mikawa

¹Department of Digestive and Cardiovascular Medicine, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan

,

Susumu Ito

¹Department of Digestive and Cardiovascular Medicine, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan

› Author Affiliations

Abstract

A dihydropyridine calcium (Ca) antagonist, azelnidipine (CAS 123524-52-7, Cal-block^®), 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 inti-ma media thickness (IMT), echocardiog-raphy, high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), 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-metaiodoben-zylguanidine myocardial scintigraphy (¹²³I-MIBG), measurements of plasma norepinephrine, atrial natriuretic peptide (ANP), and BNP, Holter electrocardiogra-phy, and heart rate variability analysis were performed.

PWV, IMT, hs-CRP, IL-6, and TNF-α significantly decreased. The levels of 8-isopros-tane, an antioxidative marker, were also significantly decreased, while adioponec-tin levels were significantly increased after the initial treatment with azelnid-ipine. After switching from amlodipine, azelnidipine exhibited a hypotensive effects comparable to amlodipine, and significantly decreased heart rate and the total number of extrasystoles. Noradrena-line 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.

Key words

Key words

Antiarteriosclerotic drugs - Autonomic nervous activity - Azelnidipine - Cardiac hypertrophy - CAS 123524-52-7 - Essential hypertension