title: Azelnidipine attenuates glomerular damage in Dahl salt-sensitive rats by suppressing sympathetic nerve activity.
abstract: 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.
authors.affiliation: Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Nagasu
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Sohachi
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Naruya
authors.initials: N
authors.lastname: Tomita
authors.forename: Tamaki
authors.initials: T
authors.lastname: Sasaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Kashihara
mesh_terms: D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D017311:Amlodipine; D001383:Azetidinecarboxylic Acid; C061679:azelnidipine