title: Effect of azelnidipine and amlodipine on single cell mechanics in mouse cardiomyocytes.
abstract: Azelnidipine and amlodipine are dihydropyridine-type Ca(2+) channel blockers for the treatment of hypertension. Although these drugs have high vasoselectivity and small negative inotropic effects in vivo, little is known regarding their direct effects on cellular contractility without humoral regulation or the additive effects of these drugs with other antihypertensive drugs on myocardial contractility. To investigate the effects of Ca(2+) channel blockers on single cell mechanics, mouse cardiomyocytes were enzymatically isolated, and a pair of carbon fibers was attached to opposite cell-ends to stretch the cells. Cells were paced at 4 Hz superfused in normal Tyrode solution at 37°C. Cell length and active/passive force calculated from carbon fiber bending were recorded in 6 different preload conditions. Slopes of end-systolic force-length relation curves (maximum elastance) were measured as an index of contractility before and after drugs were administered. Azelnidipine at 10nM and 100 nM did not change maximum elastance, while amlodipine at 100 nM did decrease maximum elastance. The combination of RNH-6270 (active form of angiotensin II receptor blocker, olmesartan, 10nM) and either amlodipine (10nM) or azelnidipine (10nM) did not affect maximum elastance. Although both amlodipine and azelnidipine can be used safely at therapeutically relevant concentrations even in combination with olmesartan, the present results suggest that azelnidipine has a less negative inotropic action compared to amlodipine.
authors.affiliation: Department of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan. iribe@okayama-u.ac.jp
authors.forename: Gentaro
authors.initials: G
authors.lastname: Iribe
authors.forename: Keiko
authors.initials: K
authors.lastname: Kaihara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Keiji
authors.initials: K
authors.lastname: Naruse
mesh_terms: D017311:Amlodipine / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001696:Biomechanical Phenomena / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004347:Drug Interactions; D007093:Imidazoles / Q000494:pharmacology; D055595:Mechanical Phenomena; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D059010:Single-Cell Analysis; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007093:Imidazoles; D013777:Tetrazoles; D017311:Amlodipine; D001383:Azetidinecarboxylic Acid; C437965:olmesartan; C061679:azelnidipine
keywords: Carbon fiber; Force—length relation; Maximum elastance; Stretch