Cardiovascular effects of azelnidipine in comparison with those of amlodipine assessed in the halothane-anaesthetized dog.
Azelnidipine is a new dihydropyridine Ca(2+) channel blocker with long plasma half-life. To understand the in vivo cardiovascular profile of azelnidipine, it was assessed in the halothane-anaesthetized, closed-chest canine model and compared with the effect of amlodipine. We administered azelnidipine in doses of 10, 20 and 70 microg/kg, i.v. or amlodipine in doses of 30, 70 and 200 microg/kg, i.v. cumulatively to the animals. The hypotensive effects of azelnidipine and amlodipine were slow in onset and long-lasted, while their extents of dose-related hypotensive effects were similar. Azelnidipine hardly affected the heart rate or plasma noradrenaline concentration at any doses, whereas the high dose of amlodipine increased these parameters. Azelnidipine as well as amlodipine tended to increase the ventricular contraction, which did not achieve statistical significance. During autonomic receptor blockade with atropine and propranolol, neither drug affected the heart rate, ventricular contraction or plasma noradrenaline concentration, although a more significant hypotensive action was observed. These results indicate that azelnidipine and amlodipine do not directly affect cardiac function. Amlodipine may induce sinus tachycardia via reflex-mediated increase in sympathetic tone. Such lack of reflex tachycardia with azelnidipine will provide potential therapeutic strategy for treatment of patients with cardiovascular diseases, being more beneficial than amlodipine.
Ishizaka
Tomomichi
T
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
Takahara
Akira
A
Iwasaki
Hiroshi
H
Mitsumori
Yoshitaka
Y
Kise
Hiroaki
H
Nakamura
Yuji
Y
Sugiyama
Atsushi
A
D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006221:Halothane / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood
D018685:Anesthetics, Inhalation; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D017311:Amlodipine; D001383:Azetidinecarboxylic Acid; C061679:azelnidipine; D006221:Halothane; D009638:Norepinephrine