cGMP analogues reduced force of contraction in cardiac muscle from wild-type mice but not from cGKI-null mutants, demonstrating that cGKI mediates the negative inotropic effect of cGMP.
cGMP-dependent protein kinase I (cGKI) is required to mediate 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 et al. (2002) studied Cardiac contractility. cGMP analogues (8-Br-cGMP and 8-pCPT-cGMP) vs. cGKI-null mutants was evaluated on Force of contraction (F(c)). cGMP analogues reduced force of contraction in cardiac muscle from wild-type mice but not from cGKI-null mutants, demonstrating that cGKI mediates the negative inotropic effect of cGMP.