Clinical Study with Azelnidipine in Patients with Essential Hypertension

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.

Effects of Azelnidipine plus OlmesaRTAn versus amlodipine plus olmesartan on central blood pressure and left ventricular mass index: the AORTA study

“…These results are consistent with previous reports in which azelnidipine decreased clinic-measured HR and 24-hour HR, whereas amlodipine increased both of these parameters, despite similar BP reductions 8,23. It was also reported that, after switching from amlodipine, azelnidipine exhibited hypotensive effects compared with amlodipine, and significantly decreased HR and the total number of extrasystole phases 24. Noradrenaline levels and the LF/HF ratio were significantly decreased, and the washout rate was significantly reduced on 123I-MIBG myocardial scintigraphy.…”

“…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 24. These differences in the effects of azelnidipine and amlodipine can also be explained by the finding that azelnidipine exerts stronger inhibition of sympathetic activity in the vasodilation-induced baroreceptor reflex than does amlodipine 7…”

A New Baroreceptor Sensitivity-Restoring Ca-Channel Blocker Diminishes Age-Related Morning Blood Pressure Increase in Hypertensive Patients: Open-Label Monitoring of Azelnidipine Treatment for Hypertension in the Early Morning (At-HOME) Study

“…Impaired BRS due to modified predominant alpha-sympathetic activity and increased arterial stiffness in the elderly may be a key physiological mechanism of increased ME-Dif [20]. AZ has been shown to ameliorate BRS [13] and to inhibit sympathetic nervous activity via vasodilation-induced baroreceptor reflex [12]. The improvement of the age-related increase in ME-Dif after treatment with AZ as observed in the present study is considered due to these known actions of this agent.…”

“…Although it is known that some CCB agents decrease BP very rapidly resulting in enhanced sympathetic activity by baroreceptor reflex and increased pulse rate, conversely, since AZ suppresses sympathetic nervous activity this agent does not induce reflex tachycardia [12]. Thus AZ-induced decrease of pulse rate possibly contributes to improvement of BRS by this agent.…”

“…Azelnidipine (AZ, Calblock, Figure 1) is a novel long-acting dihydropyridine Ca-channel blocker (CCB) that exerts potent and long-lasting BP-lowering activity for 24 h [9] and reduces heart rate compared with other CCBs such as amlodipine [10,11]. These actions of AZ are considered due to inhibitory effects on sympathetic nervous activity [12]. We also previously demonstrated that AZ ameliorates BRS in hypertensive patients [13].…”