Roles of cGMP-dependent protein kinase I (cGKI) and PDE5 in the regulation of Ang II-induced cardiac hypertrophy and fibrosis

It has been reported that elevation of cGMP and activation of cGMP-dependent protein kinase I (cGKI) by inhibition of PDE5 activity with sildenafil prevents cardiac hypertrophy. We studied the roles of cGKI and PDE5 inhibition on angiotensin (AII)-induced hypertrophy and fibrosis using control (Ctr) mice and mice expressing cGKI only in cells where the smooth muscle SM22α promotor is active (βRM). In Ctr mice, sildenafil did not reduce the AII-induced increase of cardiomyocyte (CM) size or myocyte hypertrophic markers but did reduce fibrosis. In βRM mice, sildenafil had little or no effect on markers of fibrosis. These results show that the sildenafil/cGMP/cGKI cascade can have an inhibitory effect on cardiac fibrosis but not on CM hypertrophy.