Dual actions of cilnidipine in human internal thoracic artery: Inhibition of calcium channels and enhancement of endothelial nitric oxide synthase

Li Fan, Qin Yang, Xiao Qiu Xiao, Kevin L. Grove, Yu Huang, Zhi Wu Chen, Anthony Furnary, Guo Wei He

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Objective: Cilnidipine is a novel, long-action L/N-type dihydropyridine calcium channel blocker that has recently been used for antihypertensive therapy. We investigated the vasorelaxation effect of cilnidipine with regard to its calcium channel blockage and nitric oxide-cyclic guanosine monophosphate-dependent mechanism in human internal thoracic artery. Methods: Fresh human internal thoracic arteries taken from discarded tissues of patients undergoing coronary artery bypass surgery were studied. Concentration-relaxation curves for cilnidipine in comparison with nifedipine were studied. The expression level of endothelial nitric oxide synthase mRNA was assayed by quantitative real-time polymerase chain reaction, and the phosphorylation of endothelial nitric oxide synthase at Ser1177 was determined by Western blotting analysis. Results: Cilnidipine and nifedipine caused nearly full relaxation in potassium-precontracted internal thoracic artery. Pretreatment with cilnidipine at the clinical plasma concentration significantly depressed the maximal contraction. Endothelium denudation (47.7% ± 7.0%, P < .05) and inhibition of endothelial nitric oxide synthase (48.6% ± 6.1%, P < .05) or guanylate cyclase (41.6% ± 3.8%, P < .01) significantly reduced the cilnidipine-induced endothelium-dependent relaxation (73.9% ± 6.4%). Cilnidipine increased the expression of endothelial nitric oxide synthase mRNA by 42.4% (P < .05) and enhanced phosphorylation level of endothelial nitric oxide synthase at Ser1177 by 37.0% (P < .05). Conclusions: The new generation of calcium channel antagonist cilnidipine relaxes human arteries through calcium channel antagonism and increases production of nitric oxide by enhancement of endothelial nitric oxide synthase. The dual mechanisms of cilnidipine in human arteries demonstrated in this study may prove particularly important in vasorelaxing therapy in cardiovascular diseases.

Original languageEnglish (US)
Pages (from-to)1063-1069
Number of pages7
JournalJournal of Thoracic and Cardiovascular Surgery
Volume141
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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