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Vasomotor Dysfunction in the Mesenteric Artery after Organ Culture with Cyclosporin A
Author(s) -
Zheng JianPu,
Zhang Xuemei,
Wang Hao,
Wang Yunman,
Cheng Zhuoan,
Yin Peihao,
Peng Wen
Publication year - 2013
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12105
Subject(s) - myograph , mesenteric arteries , vasomotor , vasodilation , medicine , organ culture , contraction (grammar) , receptor , endothelin receptor , pharmacology , nitric oxide , vasoconstriction , endothelium , artery , endocrinology , vascular smooth muscle , in vitro , biology , smooth muscle , biochemistry
Cyclosporin A (CsA) is a widely used immunosuppressive agent that also causes hypertension. However, the molecular basis for CsA‐induced hypertension remains elusive. In this study, we established an in vitro model for CsA‐induced pathological changes in vasculature. Rat mesenteric arteries were incubated with CsA for 24 hr in an organ culture system. Both vasocontraction and vasorelaxation in mesenteric artery were studied using myograph technology, and mRNA expressions of the contractile receptors were determined by real‐time PCR. The results showed that CsA increased the mRNA expression and contractile function of several G‐protein‐coupled receptors (GPCRs), such as endothelin receptor type B (ET B ), 5‐hydroxytryptamine type 1B (5‐HT 1B ) and 1D (5‐HT 1D ), in vascular smooth muscle cells. In addition, both nitric oxide (NO)‐mediated vasorelaxation and endothelium‐independent relaxation were impaired by CsA. In summary, this study showed the enhanced GPCRs‐mediated contraction and reduced vasorelaxation in mesenteric artery after organ culture with CsA, which mimicked the CsA‐induced pathological changes in the vascular system in vivo . Furthermore, this organ culture system would be an ideal in vitro tool to study the molecular mechanisms of CsA‐induced hypertension.