cGMP-dependent protein kinase I mediates the negative inotropic effect of cGMP in the murine myocardium.
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.
Wegener
Jörg W
JW
Pharmakologisches Institut, Universität Mainz, Germany.
Nawrath
Hermann
H
Wolfsgruber
Wiebke
W
Kühbandner
Susanne
S
Werner
Claudia
C
Hofmann
Franz
F
Feil
Robert
R
D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology
D013873:Thionucleotides; C016276:8-bromocyclic GMP; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP