In Vitro Assessment of Clevidipine Using the Profilin1 Hypertensive Mouse Model
نویسندگان
چکیده
Hypertension represents a major risk factor for cardiovascular events, associating with vascular hypertrophy and dysfunction in resistance vessels. Clevidipine is a novel antihypertensive drug working as a selective calcium channel antagonist with an ultra-short half-life that lowers arterial blood pressure by reducing systemic arterial resistance. The aim was to assess the effect of clevidipine on the hypertrophic vessels of profilin1 hypertensive transgenic mice compared to sodium nitroprusside (SNP) and labetalol using wire myograph techniques. The effects of clevidipine, SNP and labetalol on the hypertrophic vessels were studied on mesenteric arterial function from 8 profilin1 hypertrophic mice and eight non-transgenic controls. Our results showed a significant difference between the effects of the three drugs on the hypertrophic mesenteric arteries of transgenic profilin1 mice compared to the non-transgenic controls. The half maximal effective concentration (EC50) of clevidipine, SNP and labetalol in profilin1 mice (1.90 ± 0.05, 0.97 ± 0.07, 2.80 ± 0.05 nM, respectively) were significantly higher than the EC50 in non-transgenic controls (0.91 ± 0.06, 0.32 ± 0.06, 0.80 ± 0.09 nM, respectively). Moreover, the increase in the EC50 for clevidipine (2-fold) to produce the same effect on both normal and hypertrophic arteries was less than that of SNP (3-fold) and labetalol (3.5-fold). Therefore, we concluded clevidipine exhibited the lowest dose shift to relax the hypertrophic vessels compared to SNP and labetalol in the profilin1 hypertrophic animal mouse model.
منابع مشابه
Mutant Profilin1 Aggregation in Amyotrophic Lateral Sclerosis: An in Vivo Biochemical Analysis
Introduction: Profilin1 (PFN1) is a ubiquitously expressed protein known for its function as a regulator of actin polymerization and dynamics. A recent discovery linked mutant PFN1 to Amyotrophic Lateral Sclerosis (ALS), which is a fatal and progressive motor neuron disease. We have also demonstrated that Gly118Val mutation in PFN1 is a cause of ALS, and the formation of aggregates containing m...
متن کاملVascular hypertrophy-associated hypertension of profilin1 transgenic mouse model leads to functional remodeling of peripheral arteries.
Increased mechanical stress/hypertension in the vessel wall triggers the hypertrophic signaling pathway, resulting in structural remodeling of vasculature. Vascular hypertrophy of resistance vessels leads to reduced compliance and elevation of blood pressure. We showed before that increased expression of profilin1 protein in the medial layer of the aorta induces stress fiber formation, triggeri...
متن کاملGenetically Engineered Mouse Embryonic Stem Cell – derived Cardiomyocytes as a Suitable Model on Drugs Toxicity In vitro
Background DOX is a powerful chemotherapeutic agent used in the treatment of solid tumors and malignant hematological diseases. However, its cardiac toxicity limits the clinical usefulness of this drug. Previous reports have shown Corticosteroids induce a cytoprotective effect on cardiomyocytes. Mouse transgenic embryonic stem cell-derived pure cardiomyocytes may be considered as a model for a...
متن کاملMorphology and Ultrastructure of Mouse Polarized Endometrial Epithelial Cell Monolyer in Vitro
Purpose: The objective for this study is to investigate the morphology and ultrastructure of mouse endometrial epithelial cell monolayer cultured on matrigel in dual-chambered system as an in vitro mouse endometrial epithelial cell culture model that mimics structural and functional properties of the endometrial epithelium in vivo. Materials and Methods: Mouse endometrial epithelial cells were...
متن کاملClevidipine for hypertensive emergency.
Hypertensive emergency, is the most severe presentation of arterial hypertension, having high morbidity-mortality. Clevidipine is a calcium channel blocker. Its pharmacokinetics is favorable to use for hypertensive emergencies, rendering this drug a promising alternative to the restricted therapeutic armamentarium available both in the emergency room and intensive care unit. In this review we d...
متن کامل