Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes.
It has been suggested that cGMP kinase I (cGKI) dampens cardiac hypertrophy. We have compared the effect of isoproterenol (ISO) and transverse aortic constriction (TAC) on hypertrophy in WT [control (CTR)] mice, total cGKI-KO mice, and cGKIbeta rescue mice (betaRM) lacking cGKI specifically in cardiomyocytes (CMs). Infusion of ISO did not change the expression of cGKI in the hearts of CTR mice or betaRM but raised the heart weight by approximately 20% in both. An identical hypertrophic growth response was measured in CMs from CTR mice and betaRM and in isolated adult CMs cultured with or without 1 muM ISO. In both genotypes, ISO infusion induced similar changes in the expression of hypertrophy-associated cardiac genes and significant elevation of serum atrial natriuretic peptide and total cardiac cGMP. No differences in cardiac hypertrophy were obtained by 7-day ISO infusion in 4- to 6-week-old conventional cGKI-KO and CTR mice. Furthermore, TAC-induced hypertrophy of CTR mice and betaRM was not different and did not result in changes of the cGMP-hydrolyzing phosphodiesterase activities in hypertropic hearts or CMs. These results strongly suggest that cardiac myocyte cGKI does not affect the development of heart hypertrophy induced by pressure overload or chronic ISO infusion.
Lukowski
Robert
R
Forschergruppe 923 and Institut für Pharmakologie und Toxikologie, Technische Universität München, D-80802 Munich, Germany. robert.lukowski@uni-tuebingen.de
Rybalkin
Sergei D
SD
Loga
Florian
F
Leiss
Veronika
V
Beavo
Joseph A
JA
Hofmann
Franz
F
D000818:Animals; D001483:Base Sequence; D006332:Cardiomegaly / Q000201:enzymology* / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D002478:Cells, Cultured; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000172:deficiency* / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000201:enzymology* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D017931:DNA Primers; D012333:RNA, Messenger; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; C569720:Prkg1 protein, mouse; D007545:Isoproterenol