Vasomotor Dysfunction in the Mesenteric Artery after Organ Culture with Cyclosporin A. (16th July 2013)

• Record Type: Journal Article
• Authors: Zheng, Jian‐Pu; Zhang, Xuemei; Wang, Hao; Wang, Yunman; Cheng, Zhuoan; Yin, Peihao; Peng, Wen
• Is Part Of: Basic & clinical pharmacology & toxicology. Volume 113:Number 6(2013)
• Page Start: 370
• Page End: 376
• Publication Date: 2013-07-16
• Subjects: Pharmacology -- Periodicals; Toxicology -- Periodicals; Pharmacology -- Periodicals; Toxicology -- Periodicals; Pharmacology, Clinical -- Periodicals; Computer network resources; Electronic journals; 615.1
• DOI: 10.1111/bcpt.12105
• Languages: English
• ISSNs: 1742-7835

Abstract

<abstract abstract-type="main" id="bcpt12105-abs-0001"> <title>Abstract</title> <p>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 <italic>in vitro</italic> 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 <italic>in vivo</italic>. Furthermore, this organ culture system would be an ideal <italic>in vitro</italic> tool to study the molecular mechanisms of CsA‐induced hypertension.</p> </abstract>