Interaction between the opposing functional effects of cyclic AMP and cyclic CMP in hypertrophic cardiac myocytes

We tested the hypothesis that in isolated cardiac myocytes, the negative fu nctional effects of cyclic GMP would be blunted when the level of cyclic AM P was increased and that this interaction would be altered in renal hyperte nsive (One-Kidney-One-Clip, 1K1C) cardiac hypertrophic rabbits. Using isola ted control and 1K1C ventricular myocytes, cyclic AMP and cell shortening ( %) data were collected: 1) at baseline, 2) after the addition of 8-Br-cGMP 10(-7) (-6) (-5) M, and 3) after forskolin (10(-6) M), an adenylate cyclase activator, followed by 8-Br-cGMP 10-7 -6 -5 M. Basal levels of cyclic AMP were similar in control vs. 1K1C myocytes (10.2 +/- 1.6 vs. 11.3 +/- 2.6 pm ol/10(5) myocytes). We found that 8-Br-cGMP decreased the percent shortenin g in a dose related manner in both control myocytes (5.1 +/- 0.6 to 3.2 +/- 0.4 %) and hypertrophic myocytes (5.2 +/- 0.4 to 3.6 +/- 0.5). The level o f cyclic AMP significantly increased after the addition of 8-Br-cGMP in con trol myocytes (14.1 +/- 2.1), but not in 1K1C myocytes. Forskolin increased the percent shortening in the control myocytes (3.8 +/- 0.1 to 4.8 +/- 0.4 ), but no significant increase was noted in the hypertrophic myocytes (3.6 +/- 0.3 to 3.7 +/- 0.3). The level of cyclic AMP significantly increased af ter the addition of forskolin in both control (13.9 +/- 2.0), and 1K1C cell s (14.6 +/- 3.8). Forskolin attenuated the negative functional effects of 8 -Br-cGMP in the control (4.8 +/- 0.4 to 3.2 +/- 0.1) and 1K1C myocytes (3.7 +/- 0.3 to 2.7 +/- 0.3). The addition of 8-Br-cGMP did not affect the leve l of cyclic AMP after forskolin in either control (13.9 +/- 2.0 to 14.8 +/- 2.5) or 1K1C myocytes (14.6 +/- 3.8 to 13.8 +/- 1.9). These data indicated that in hypertrophic cardiac myocytes the negative functional effects of 8 -Br-cGMP were similar to control, but the positive functional effects of cy clic AMP were blunted. There was an increase in cyclic AMP levels after add ition of 8-Br-cGMP in control but not 1K1C cells. We conclude that in contr ol and hypertrophic myocytes, the effects of cyclic GMP were blunted after forskolin, but this did not seem to be related to cyclic AMP phosphodiester ase activity.