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Morphine-mediated alteration of hypertension-related gene expression in human white blood cells and multilineage progenitor cells

Journal of Human Hypertension volume 24, pages 713–720 (2010)Cite this article

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Abstract

It has been shown that vascular endothelial cells functionally express a local circuit autocrine–paracrine regulatory pathway driven by endogenously expressed chemically authentic morphine, its cognate opiate alkaloid-selective mu3 and mu4 receptors, and constitutive nitric oxide (NO). Accordingly, the aim of the study was to examine morphine-mediated changes in hypertension-associated gene expression in two independent cell models: primary cultures of human white blood cells (WBCs) and human multilineage progenitor cells (MLPCs). In separate incubations, primary cultures of human WBC and MLPC were treated with morphine at a final concentration of 1 μ morphine for 2–4 h. After RNA extraction and reverse transcription, Human Genome Survey Arrays were used to construct and differentially analyze by strict statistical criteria transcriptional/gene expression profiles of WBC and undifferentiated human MLPC in three independent experiments. The Applied Biosystems Human Genome Survey Array contains 31 700 60-mer oligonucleotide probes representing a set of 27 868 individual human genes and >1000 control probes. After DNA microarray analyses, a variety of hypertension-associated genes from both cell types were observed to be significantly downregulated. The only genes expressed in both cell types were β-adrenergic receptor kinase 2 (ADRBK2) and coding protein kinase WNK1 (PRKWNK1); however, only PRKWNK1 showed downregulation of its expression after morphine exposure. Only two genes were observed to be significantly upregulated after morphine treatment: ADRBK2 in stem cells and β3-adrenergic receptor in WBC. Morphine administration to primary cultures of human WBC and MLPC altered the expression profile of 16 candidate hypertension-associated genes. The majority of relevant genes was observed to be downregulated, suggesting ongoing homeostatic regulation by endogenous morphine coupled to NO production and release. In sum, these data suggest a predominantly antihypertensive role for endogenous morphine/NO signaling events.

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Authors and Affiliations

  1. Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland

    M Banach

  2. Neuroscience Research Institute, State University of New York—College at Old Westbury, Old Westbury, NY, USA

    F M Casares, R M Kream & G B Stefano

  3. Department of Nephrology, Hypertension and Family Medicine, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland

    A Gluba & J Rysz

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  1. M Banach
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Correspondence to G B Stefano.

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Banach, M., Casares, F., Kream, R. et al. Morphine-mediated alteration of hypertension-related gene expression in human white blood cells and multilineage progenitor cells. J Hum Hypertens 24, 713–720 (2010). https://doi.org/10.1038/jhh.2010.69

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