Mechanisms related to atorvastatin and insulin administration on nitric oxide production and vasodilation in vascular endothelial cells
Mechanisms related to atorvastatin and insulin administration on nitric oxide production and vasodilation in vascular endothelial cells
Ali Nosrati Andevari,1,*Durdi Qujeq,2
1. Department of Clinical Biochemistry, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran 2. Department of Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran
Introduction: Vascular endothelial cells play an important role in cardiovascular disorders. Atorvastatin is a oral medicine that reduces blood cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-R), thereby reducing endothelial cell damage. Subcutaneous insulin administration reduces blood glucose levels and vascular complications in hyperglycemic patients. NO is a factor produced in endothelial cells by endothelial nitric oxide synthase (eNOS). NO is critical to vasodilation. The aim of this study was to evaluate the mechanisms related to atorvastatin and insulin administration on nitric oxide production and vasodilation in vascular endothelial cells.
Methods: For this review, 40 articles were found in the first stage. Strategy search in this case was as follows: the first five words (atorvastatin, insulin, nitric oxide, vasodilation, and endothelial cells) in the mesh PubMed dataset were initially identified. Then, we combined five words in the pattern of using AND and OR. In this study, human, animal, and in vitro studies were conducted were used.
Results: According to the conducted studies, atorvastatin is a lipophilic statin that easily passes through vascular endothelial cells. It increases eNOS mRNA stability and eNOS protein activity by inhibiting the RhoA/ROCK signaling pathway. Insulin increases eNOS activity by activating the PI3K/PDK1/AKT pathway. NO leads to vasodilation by activating cGMP-dependent protein kinase (PKG). In addition, PKG inhibits the RhoA/ROCK pathway.
Conclusion: Atorvastatin and insulin activate mechanisms in vascular endothelial cells, leading to increased NO production, decreased vasoconstriction, and increased vasodilation.