Journal
CIRCULATION RESEARCH
Volume 90, Issue 1, Pages 18-20Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/hh0102.103222
Keywords
mouse; gene targeting; Cre recombinase
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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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