Inhibition of sustained hypoxic vasoconstriction by Y-27632 in isolated intrapulmonary arteries and perfused lung of the rat

T P Robertson, M Dipp, J P T Ward, P I Aaronson, A M Evans

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    141 Citations (Scopus)

    Abstract

    We have examined the effects of Y-276321 a specific inhibitor of Rho-activated kinases (ROCK I and ROCK II) upon sustained hypoxic pulmonary vasoconstriction (HPV) in both rat isolated small intrapulmonary arteries (IPA) and perfused rat lungs in situ. Y-27632 (100 nM-3 mu M) was found to cause a concentration-dependent inhibition of acute sustained HPV in rat IPA. Application of Y-27632 (10-600 nM) in perfused rat lungs caused no change in basal perfusion pressure, but was found to inhibit HPV in a concentration-dependent manner, resulting in complete ablation of the presser response to hypoxia at a concentration of 600 nM. Furthermore, addition of Y-27632 at any point during hypoxia caused a reversal of HPV in perfused rat lungs. These results suggest that activation of Rho-associated kinase may be a pivotal step in the generation of sustained HPV.
    Original languageEnglish
    Pages (from-to)5 - 9
    Number of pages5
    JournalBritish Journal of Pharmacology
    Volume131
    Issue number1
    DOIs
    Publication statusPublished - 2000

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