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Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications
Hai-Tao Hou1, Jun Wang2, Zheng-Qing Wang2
1Center for Basic Medical Research and Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Tianjin, China; The Affiliated Hospital of Hangzhou Normal University and Zhejiang University, Hangzhou, China.
Insights
Benidipine, a calcium channel blocker, effectively reduces vasoconstriction in the internal mammary artery (IMA) during coronary artery bypass grafting (CABG). This study shows benidipine
Area of Science:
- Cardiovascular Pharmacology
- Vascular Biology
- Surgical Research
Background:
- Graft spasm is a significant challenge in coronary artery bypass grafting (CABG).
- Calcium antagonists are frequently used for coronary artery disease management.
- The efficacy of benidipine in preventing internal mammary artery (IMA) vasoconstriction requires investigation.
Purpose of the Study:
- To investigate the inhibitory effect of benidipine on vasoconstriction in the human IMA.
- To evaluate benidipine's vasorelaxant and antispastic potential in CABG grafts.
Main Methods:
- Human IMA rings (N=65) from 37 patients undergoing CABG were studied using a myograph.
- Relaxing effects of benidipine on KCl- and U46619-induced precontraction were assessed.
- Enzyme-linked immunosorbent assay (ELISA) measured changes in L-type calcium channel protein.
Main Results:
- Benidipine demonstrated greater relaxation in KCl-contracted (86.7%) than U46619-contracted (63.8%) IMA rings.
- Pretreatment with benidipine significantly reduced KCl-induced contraction (p < 0.05) but not U46619-induced contraction.
- Benidipine also decreased caveolin (CaV)1.2 protein content (p < 0.05).
Conclusions:
- Benidipine exhibits potent inhibitory effects on vasoconstriction in the human IMA.
- Its use in CABG patients may offer vasorelaxant and antispastic benefits for grafts.
Background:
Graft spasm remains challenging in coronary artery bypass grafting (CABG). Calcium antagonists are commonly used in patients with coronary artery disease. This study investigated the inhibitory effect of third-generation dihydropyridine calcium channel antagonist benidipine on the vasoconstriction induced by various vasoconstrictors in the human internal mammary artery (IMA).
Methods:
Isolated human IMA rings (N = 65, taken from 37 patients undergoing CABG) were studied in a myograph in 2 ways: the relaxing effect of benidipine on vasoconstrictor-induced precontraction by KCl and U46619 and the depressing effect of benidipine at plasma concentrations on the contraction. Enzyme-linked immunosorbent assay (ELISA) was used to measure the change of the protein related to the L-type calcium channel.
Results:
Benidipine caused more relaxation in KCl-contracted (86.7% ± 3.3%; n = 12) than in U46619-contracted (63.8% ± 5.3%; n = 8; p < 0.001) IMA rings. Pretreatment of IMA with plasma concentrations of benidipine (-6.92 log M) significantly depressed subsequent contraction by KCl (from 17.3 ± 2.7 mN to 7.4 ± 1.2 mN; n = 6; p < 0.05) but did not significantly affect the contraction caused by U46619. Benidipine also caused a decrease of caveolin (CaV)1.2 protein content (0.55 ± 0.02 versus 0.63 ± 0.02 mg/mL; p < 0.05).
Conclusions:
We conclude that in human IMA, the third-generation dihydropyridine calcium channel antagonist benidipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Use of benidipine in patients undergoing CABG may provide vasorelaxant or antispastic effects in the grafts.
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