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      cGMP-dependent protein kinase I mediates the negative inotropic effect of cGMP in the murine myocardium.

      Circulation Research

      pharmacology, Cyclic GMP, analogs & derivatives, Cyclic GMP-Dependent Protein Kinases, genetics, metabolism, Genotype, Mice, Animals, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Knockout, Myocardial Contraction, drug effects, Myocardium, enzymology, Thionucleotides

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          Abstract

          To study the role of cGMP-dependent protein kinase I (cGKI) for cardiac contractility, force of contraction (F(c)) was studied in electrically driven heart muscle from wild-type (WT) mice and from conventional and conditional cGKI knockout mice. Both 8-Br-cGMP and 8-pCPT-cGMP reduced Fc in cardiac muscle from juvenile WT but not from juvenile cGKI-null mutants. Similarly, the cGMP analogues reduced F(c) in forskolin-stimulated ventricular muscle from WT mice but not from cGKI-null mutants. In contrast, carbachol reduced F(c) in both groups of animals. 8-Br-cGMP reduced F(c) also in heart muscle from adult WT mice but not from adult cardiomyocyte-specific cGKI-knockout mice. These results demonstrate that cGKI mediates the negative inotropic effect of cGMP in the myocardium of juvenile and adult mice.

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          11786513

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