Reduction in interaction between cGMP and cAMP in dog ventricular myocytes with hypertrophic failure

Baseline function and signal transduction are depressed in hearts with hypertrophic failure. We tested the hypothesis that the effects of cGMP and its interaction with cAMP would be reduced in cardiac myocytes from hypertrophic failing hearts. Ventricular myocytes were isolated from control dogs, dogs with aortic valve stenosis hypertrophy, and dogs with pacing hypertrophic failure. Myocyte function was measured using a video edge detector. Cell contraction data were obtained at baseline, with 8-bromo-cGMP (10−7, 10−6, and 10−5 M), with erythro-9-(2-hydroxy-3-nonyl)adenine [EHNA; a cAMP phosphodiesterase (PDE2) inhibitor] plus 8-bromo-cGMP, or milrinone (a PDE3 inhibitor) plus 8-bromo-cGMP. Baseline percent shortening and maximal rates of shortening (Rmax) and relaxation were slightly reduced in hypertrophic myocytes and were significantly lower in failing myocytes (Rmax: control dogs, 95.3 ± 17.3; hypertrophy dogs, 88.2 ± 5.5; failure dogs, 53.2 ± 6.4 μm/s). 8-Bromo-cGMP dose dependently reduced myocyte ...