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OtherPULMONARY PHARMACOLOGY

Phosphodiesterase Isoforms in the Pulmonary Arterial Circulation of the Rat: Changes in Pulmonary Hypertension

M. R. Maclean, E. D. Johnston, K. M. Mcculloch, L. Pooley, M. D. Houslay and G. Sweeney
Journal of Pharmacology and Experimental Therapeutics November 1997, 283 (2) 619-624;
M. R. Maclean
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E. D. Johnston
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K. M. Mcculloch
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L. Pooley
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M. D. Houslay
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G. Sweeney
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Abstract

Phosphodiesterase (PDE) activity was determined in pulmonary arteries removed from control and chronic hypoxia-induced pulmonary hypertensive rats. The main, first-branch, intrapulmonary and resistance pulmonary arteries were studied. We measured total cAMP PDE activity and cGMP PDE activity, as well as that of individual isoforms (PDE1–5). cAMP PDE activity in chronic hypoxic rats was increased in first-branch and intrapulmonary arteries from hypoxic rats. No changes were observed in the main or resistance pulmonary arteries. Similarly, cGMP PDE activity was increased in the main, first-branch and intra-pulmonary arteries of the hypoxic rats. No changes in cGMP PDE activity were observed in resistance arteries. There was evidence for PDE1–5 activity in all pulmonary arteries. The increased cAMP PDE activity in first-branch and intrapulmonary vessels was associated with an increase in cilostimide-inhibited PDE (PDE3) activity. Increased total cGMP PDE in main pulmonary artery was associated with increases in Ca++/calmodulin-stimulated (PDE1) activity. An increase in zaprinast-inhibited (PDE5) activity was observed in first-branch and intrapulmonary arteries. Our results suggest that decreases in intracellular cyclic nucleotide levels in pulmonary arteries from pulmonary hypertensive rats are associated with increased PDE activity. Further, these changes may reflect alterations at the level of specific types of PDE isoforms.

Footnotes

  • Send reprint requests to: Margaret R. MacLean, Pulmonary Research Group, Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland.

  • ↵1 This work was supported by The Wellcome Trust, UK, and The Medical Research Council, UK.

  • Abbreviations:
    PDE
    phosphodiesterase
    EHNA
    erythro-9-(2-hydroxy-3-nonyl) adenine
    PHT
    pulmonary hypertension
    LV
    left ventricle
    RV
    right ventricle, TV, total ventricle
    PMSF
    phenylmethylsulfonyl fluoride
    EDRF
    endothelium-derived relaxing factor
    IBMX
    isobutylmethylxanthine
    • Received April 24, 1997.
    • Accepted July 11, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 283, Issue 2
1 Nov 1997
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OtherPULMONARY PHARMACOLOGY

Phosphodiesterase Isoforms in the Pulmonary Arterial Circulation of the Rat: Changes in Pulmonary Hypertension

M. R. Maclean, E. D. Johnston, K. M. Mcculloch, L. Pooley, M. D. Houslay and G. Sweeney
Journal of Pharmacology and Experimental Therapeutics November 1, 1997, 283 (2) 619-624;

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OtherPULMONARY PHARMACOLOGY

Phosphodiesterase Isoforms in the Pulmonary Arterial Circulation of the Rat: Changes in Pulmonary Hypertension

M. R. Maclean, E. D. Johnston, K. M. Mcculloch, L. Pooley, M. D. Houslay and G. Sweeney
Journal of Pharmacology and Experimental Therapeutics November 1, 1997, 283 (2) 619-624;
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