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      Involvement of cGMP-dependent protein kinase in the relaxation of ovine pulmonary arteries to cGMP and cAMP.

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          Abstract

          Agonist-induced smooth muscle relaxation occurs following an increase in intracellular concentrations of cGMP or cAMP. However, the role of protein kinase G (PKG) and/or protein kinase A (PKA) in cGMP- or cAMP-mediated pulmonary vasodilation is not clearly elucidated. In this study, we examined the relaxation responses of isolated pulmonary arteries of lambs (age = 10 +/- 1 days), preconstricted with endothelin-1, to increasing concentrations of 8-bromo-cGMP (8-BrcGMP) or 8-BrcAMP (cell-permeable analogs), in the presence or absence of Rp-8-beta-phenyl-1,N(2)-etheno-bromoguanosine cyclic monosphordthioate (Rp-8-PET-BrcGMPS) or KT-5720, selective inhibitors of PKG and PKA, respectively. When examined for specificity, Rp-8-Br-PET-cGMPS abolished PKG, but not PKA, activity in pulmonary arterial extracts, whereas KT-5720 inhibited PKA activity only. 8-BrcGMP-induced relaxation was inhibited by the PKG inhibitor only, whereas 8-BrcAMP-induced relaxation was inhibited by both inhibitors. A nearly fourfold higher concentration of cAMP than cGMP was required to relax arteries by 50% and to activate PKG by 50%. Our results demonstrate that relaxation of pulmonary arteries is more sensitive to cGMP than cAMP and that PKG plays an important role in both cGMP- and cAMP-mediated relaxation.

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          Author and article information

          Journal
          J. Appl. Physiol.
          Journal of applied physiology (Bethesda, Md. : 1985)
          American Physiological Society
          8750-7587
          0161-7567
          May 2000
          : 88
          : 5
          Affiliations
          [1 ] Department of Pediatrics, Harbor-UCLA Medical Center, School of Medicine, University of California, Los Angeles, Torrance, California 90509, USA. dhanakoti@humc.edu
          Article
          10.1152/jappl.2000.88.5.1637
          10797124

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