Characterization of nicardipine hydrochloride-induced cell injury in human vascular endothelial cells

The Journal of Toxicological Sciences
Masanori OchiHiromu Toyoda

Abstract

Nicardipine hydrochloride (NIC), a dihydropyridine calcium-channel blocking agent, has been widely used for the treatment of hypertension. Especially, nicardipine hydrochloride injection is used as first-line therapy for emergency treatment of abnormally high blood pressure. Although NIC has an attractive pharmacological profile, one of the dose-limiting factors of NIC is severe peripheral vascular injury after intravenous injection. The goal of this study was to better understand and thereby reduce NIC-mediated vascular injury. Here, we investigated the mechanism of NIC-induced vascular injury using human dermal microvascular endothelial cells (HMVECs). NIC decreased cell viability and increased percent of dead cells in a dose-dependent manner (10-30 μg/mL). Although cell membrane injury was not significant over 9 hr exposure, significant changes of cell morphology and increases in vacuoles in HMVECs were observed within 30 min of NIC exposure (30 μg/mL). Autophagosome labeling with monodansylcadaverine revealed increased autophagosomes in the NIC-treated cells, whereas caspase 3/7 activity was not increased in the NIC-treated cells (30 μg/mL). Additionally, NIC-induced reduction of cell viability was inhibited by 3-methyladen...Continue Reading

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Citations

Jul 18, 2016·Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association·Kei KawadaMasanori Morimoto
Oct 21, 2016·Clinical and Experimental Pharmacology & Physiology·Fan Jiang
May 5, 2018·Stroke; a Journal of Cerebral Circulation·Kyeong-A KimOk-Nam Bae
Jul 10, 2021·Autophagy·Muhammed KocakOle Pless

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