Abstract:
:Imipramine, an antidepressant drug, can cause potentially lethal cardiotoxic side effects including hypotension, ventricular tachycardia, and decreased cardiac output. This study investigated the mechanism responsible for imipramine-induced cardiac depression in rats. The left ventricular developed pressure (LVDP), velocity of the change in pressure (dP/dt), and heart rate (HR) accompanied with the total magnesium efflux ([Mg](e)) were measured in Langendorff-perfused intact rats hearts. Intracellular ionized magnesium concentrations ([Mg(2+)]( i)) were measured using Mag-fura 2 AM in a single H9c2 cell. The activation of the extracellular signal-regulated kinases 1/2 (ERK 1/2) was analyzed by Western blot. Imipramine induced reversible decreases in LVDP, dP/dt, and HR, which were accompanied by increases in [Mg](e). Imipramine also induced activation of ERK 1/2 and increase in the [Mg(2+)]( i), which was inhibited PD98059, ERK 1/2 inhibitor. These results suggest that imipramine-induced cardiac depression may be partly due to increases of [Mg(2+)](i) that are accompanied by the activation of ERK 1/2 in rats.
journal_name
J Cardiovasc Pharmacol Therjournal_title
Journal of cardiovascular pharmacology and therapeuticsauthors
Lee MY,Kim SJ,Kim JS,Kang HSdoi
10.1177/1074248410366853subject
Has Abstractpub_date
2010-09-01 00:00:00pages
303-10issue
3eissn
1074-2484issn
1940-4034pii
1074248410366853journal_volume
15pub_type
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journal_title:Journal of cardiovascular pharmacology and therapeutics
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