Hypertension Research 2012-03-01

Azelnidipine attenuates glomerular damage in Dahl salt-sensitive rats by suppressing sympathetic nerve activity.

Hajime Nagasu, Minoru Satoh, Sohachi Fujimoto, Naruya Tomita, Tamaki Sasaki, Naoki Kashihara

文献索引：Hypertens. Res. 35(3) , 348-55, (2012)

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摘要

Dihydropyridine-type calcium channel blockers (CCBs) exert potent antihypertensive effects. The CCB azelnidipine decreases heart rate by suppressing sympathetic nerve activity, which affects afferent and efferent arterioles in the glomeruli. We examined whether azelnidipine can improve progressive glomerular injury in comparison with amlodipine by suppressing renal sympathetic nerve activity in Dahl salt-sensitive rats. Glomerular circulation in Dahl salt-sensitive rats was monitored with a charge-coupled device camera before and after administration of amlodipine (0.5 mg kg(-1), bolus injection) or azelnidipine (0.1 mg kg(-1), bolus injection). Systemic sympathetic nerve activity was also compared by analysis of heart rate variability with a telemetry blood pressure monitoring system after crossover administration of amlodipine (1.0 mg kg(-1) per day) and azelnidipine (3.0 mg kg(-1) per day) for 1 week. To investigate renoprotective effects, rats were treated with amlodipine (1.0 mg kg(-1) per day) or azelnidipine (3.0 mg kg(-1) per day) for 3 weeks with or without renal denervation. The efferent arteriole contracted in response to acute amlodipine but not azelnidipine treatment. The low frequency/high frequency ratio, an index of parasympathetic nerve activity, decreased in response to azelnidipine but not amlodipine treatment. In response to chronic treatment, proteinuria and glomerular injury improved to a greater extent with azelnidipine compared with amlodipine. The renoprotective effects of azelnidipine were diminished by renal denervation. Azelnidipine decreased glomerular damage in Dahl salt-sensitive rats to a greater extent than amlodipine. Azelnidipine appeared to decrease intraglomerular pressure by suppressing sympathetic nerve activity.