1. Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications 
Hai-Tao Hou, BE, Jun Wang, BA, Zheng-Qing Wang, MD, Xiao-Cheng Liu, MD, Marija Marinko, D. Pharm, Aleksandra Novakovic, PhD, Qin Yang, MD, PhD, Guo-Wei He, MD, DS 
The Annals of Thoracic Surgery 
Volume 101, Issue 5, Pages (May 2016)
DOI: /j.athoracsur
Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

2. Fig 1
(A) Mean concentration (–log M)-relaxation curves in human internal mammary artery (IMA) for benidipine in potassium chloride–induced (KCl, 40 mM; n = 12) and U46619-induced (–8 log M; n = 8) contractions. Benidipine caused more relaxation in the KCl-induced contraction (p < 0.01). (B) Comparison between benidipine and amlodipine (n = 11) in KCl-induced contraction. Values are expressed as mean ± standard error of the mean.
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

3. Fig 2
Mean concentration (–log M)-contraction (mN) curves for KCl when benidipine –7.92 log M, –6.92 log M, or vehicle were added 30 minutes before the contraction started in the human IMA segments (n = 6). Three rings from an IMA segment taken from the same patient were allocated to each group. Values are expressed as mean ± standard error of the mean (*p < 0.05, 1-way ANOVA and compared to the control [vehicle] by Bonferroni post hoc test at maximal contraction; 2-way ANOVA was used for curves).
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

4. Fig 3
Mean concentration (–log M)-contraction (mN) curves for U46619 when benidipine –7.92 log M, –6.92 log M, or vehicle was added 30 minutes before the contraction started in the human IMA segments (n = 7). Three rings from an IMA segment taken from the same patient were allocated to each group. Values are expressed as mean ± standard error of the mean.
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

5. Fig 4
Caveolin (CaV)1.2 levels in benidipine-treated group and control group measured by enzyme-linked immunosorbent assay (ELISA). The CaV1.2 level in benidipine group was lower than that in control group (p = 0.03). Values are expressed as mean ± standard error of the mean.
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions

6. Fig 5
Molecular mechanism for benidipine relaxing human internal mammary artery (IMA) and its role in preventing smooth muscle contraction of artery. Vascular smooth muscle contraction is the summation of myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) activity. Ca2+ influx through calcium channels located in membrane (voltage-operated channel [VOC] and receptor-operated channel [ROC]) and Ca2+ release from intracellular stores in sarcoplasmic reticulum through phospholipase C–mediated hydrolysis of phosphatidylinositol bisphosphate, yielding inositol triphosphate (IP3), result increase in intracellular Ca2+. Ca2+ interacts with calmodulin, forming a Ca2+-calmodulin complex that activates MLCK, which phosphorylates MLCP, allowing for close interaction of actin and myosin filaments for force generation. Vasoconstrictors open through either ROC (thromboxane A2 [TXA2]) or VOC (potassium chloride [KCl]), causing Ca2+ influx, or through production of second messengers such as IP3, causing release of stored Ca2+. Contraction can also be mediated by Ca2+-sensitization mechanism. Benidipine mainly inhibits VOC (and to lesser extent ROC) and reduces or blocks Ca2+ influx and therefore causes relaxation or inhibition of contraction. (Ca2+ = calcium concentration; [Ca2+]i = intracellular calcium; Em = member potential.)
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions