Calcium blockers inhibit cyclosporine A-induced hyperreactivity of vascular smooth muscle cells

  • Authors:
    • Grzegorz Grześk
    • Michał Wiciński
    • Bartosz Malinowski
    • Elżbieta Grześk
    • Sławomir Manysiak
    • Grażyna Odrowąż-Sypniewska
    • Nasser Darvish
    • Maciej Bierwagen
  • View Affiliations

  • Published online on: March 26, 2012     https://doi.org/10.3892/mmr.2012.847
  • Pages: 1469-1474
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Abstract

Cyclosporine belongs to the group of the most commonly used immunosuppressants. Hypertension occurs in approximately 30% of patients treated with this drug. However, the pathogenesis of this occurrence has not been explained to date. The purpose of our study was to clarify the mechanisms leading to the evolution of hypertension induced by cyclosporine A (CsA). We examined the changes in transmission within receptors and around the receptors. We also aimed to elucidate the mechanisms responsible for averting arterial hyperresponsiveness induced by the drug. Experiments were performed on isolated and perfused tail arteries of Wistar rats. Tissues surrounding the artery were removed and the proximal segment (length of 2-3 cm) was used for cannulation. Cannulated arteries were placed in a 20-ml glass chamber (vertical position). The contraction force in our model was measured by an increased degree of perfusion pressure with a constant flow rate (approximately 1 ml/min). The results showed that in the presence of CsA, the concentration-response curves/phenylephrine (PHE) curve shifted to the left. Cyclosporine increased the reactivity of the arteries to PHE. This effect was directly linked to the increase in the receptor reserve. The analysis of the reactivity of vascular smooth muscle showed that CsA increased the influx of calcium ions from the extracellular to the intracellular area. No difference was found between the contraction triggered by Bay-K8644 in the presence of CsA and the control probe. The increase in perfusion pressure induced by CsA was blocked by L-type calcium channel blockers (nifidipine and diltiazem). The results from our experiments show that CsA increases the reactivity of vessels to the effect of catecholamines. CsA also enhances signal transmission between G-protein coupled receptors (GPCRs) and calcium channels. The activation of protein kinase C also plays a significant role in this process. Our results suggest that the best choice for the pharmacotherapy of hypertension induced by CsA would be calcium channel antagonists.

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June 2012
Volume 5 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Grześk G, Wiciński M, Malinowski B, Grześk E, Manysiak S, Odrowąż-Sypniewska G, Darvish N and Bierwagen M: Calcium blockers inhibit cyclosporine A-induced hyperreactivity of vascular smooth muscle cells. Mol Med Rep 5: 1469-1474, 2012.
APA
Grześk, G., Wiciński, M., Malinowski, B., Grześk, E., Manysiak, S., Odrowąż-Sypniewska, G. ... Bierwagen, M. (2012). Calcium blockers inhibit cyclosporine A-induced hyperreactivity of vascular smooth muscle cells. Molecular Medicine Reports, 5, 1469-1474. https://doi.org/10.3892/mmr.2012.847
MLA
Grześk, G., Wiciński, M., Malinowski, B., Grześk, E., Manysiak, S., Odrowąż-Sypniewska, G., Darvish, N., Bierwagen, M."Calcium blockers inhibit cyclosporine A-induced hyperreactivity of vascular smooth muscle cells". Molecular Medicine Reports 5.6 (2012): 1469-1474.
Chicago
Grześk, G., Wiciński, M., Malinowski, B., Grześk, E., Manysiak, S., Odrowąż-Sypniewska, G., Darvish, N., Bierwagen, M."Calcium blockers inhibit cyclosporine A-induced hyperreactivity of vascular smooth muscle cells". Molecular Medicine Reports 5, no. 6 (2012): 1469-1474. https://doi.org/10.3892/mmr.2012.847