cGMP-Dependent Protein Kinase I Mediates the Negative Inotropic Effect of cGMP in the Murine Myocardium

• Published in: Circulation research Vol. 90; no. 1; pp. 18 - 20
• Main Authors: Wegener, Jörg W, Nawrath, Hermann, Wolfsgruber, Wiebke, Kühbandner, Susanne, Werner, Claudia, Hofmann, Franz, Feil, Robert
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 11.01.2002; Lippincott; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Animals; Biological and medical sciences; Cyclic GMP - analogs & derivatives; Cyclic GMP - pharmacology; Cyclic GMP-Dependent Protein Kinases - genetics; Cyclic GMP-Dependent Protein Kinases - metabolism; Fundamental and applied biological sciences. Psychology; Genotype; Heart; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Myocardial Contraction - drug effects; Myocardium - enzymology; Myocardium - metabolism; Thionucleotides - pharmacology; Vertebrates: cardiovascular system; Heart; Enzyme; Transferases; Rodentia; Contractility; Transgenic animal; 3',5'-GMP; Signal transduction; Vertebrata; Mammalia; Mouse; Protein kinase; Myocardium; Circulatory system; Mutation
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/hh0102.103222

To study the role of cGMP-dependent protein kinase I (cGKI) for cardiac contractility, force of contraction (Fc) 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 Fc in forskolin-stimulated ventricular muscle from WT mice but not from cGKI-null mutants. In contrast, carbachol reduced Fc in both groups of animals. 8-Br-cGMP reduced Fc 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.