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Effect of azelnidipine and amlodipine on single cell mechanics in mouse cardiomyocytes
- Source :
- European Journal of Pharmacology. 715:142-146
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
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.
- Subjects :
- Inotrope
Dihydropyridines
medicine.medical_specialty
Angiotensin receptor
Azelnidipine
Tetrazoles
Pharmacology
Contractility
Angiotensin Receptor Antagonists
Mice
Internal medicine
medicine
Animals
Drug Interactions
Myocytes, Cardiac
Channel blocker
Amlodipine
Mechanical Phenomena
Chemistry
Imidazoles
Calcium Channel Blockers
Biomechanical Phenomena
Preload
Endocrinology
Single-Cell Analysis
Olmesartan
Azetidinecarboxylic Acid
medicine.drug
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 715
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....0a4af344d437cc395f85c906d595b0d2