Negative functional effects of cyclic GMP are altered by cyclic AMP phosphodiesterases in rabbit cardiac myocytes

Weiss, Harvey R.; Lazar, Michael; Punjabi, Kusum; Tse, James; Scholz, Peter

doi:10.1016/j.ejphar.2003.09.006

Cited by 6 publications

(16 citation statements)

References 26 publications

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“…Many of these effects are related to activation of the cyclic AMP-dependent protein kinase, which may phosphorylate membrane channels or parts of the contractile machinery [6,9] , as well as nonprotein kinase effects [10] . There is some evidence that nitric oxide can activate the cyclic AMP protein kinase, but this may be through effects on the cyclic GMP-affected cyclic AMP phosphodiesterases [13,25] . In the control myocytes, we found that isoproterenol dose-dependently increased myocyte function and that this was associated with an increase in the level of cyclic AMP.…”

Section: Discussionmentioning

confidence: 99%

“…Many of the actions of cyclic GMP are through changes in protein phosphorylation caused by activation of the cyclic GMP protein kinase [8,9,15] . There is also evidence that the cyclic GMP-affected cyclic AMP phosphodiesterases can play an important role in the functional effects of cyclic GMP through changes in the level of cyclic AMP in the heart and myocytes [13,14,27] . At rest, the cyclic AMP levels in control myocytes was about 15 times that of cyclic GMP, as has been reported previously [9,11,13,20,23] .…”

Section: Discussionmentioning

confidence: 99%

“…Freshly isolated ventricular myocytes were prepared by a standard method as described previously [9,13] . The control and 1K1C rabbits were anesthetized and the heart was rapidly removed after an overdose of pentobarbital (90 mg/kg).…”

Section: Cell Dissociationmentioning

confidence: 99%

“…Cyclic GMP has negative functional and metabolic effects on both the myocardium and isolated cardiac myocytes [11,12] . Many studies have also shown that cyclic GMP antagonizes the positive metabolic and functional effects of catecholamines and cyclic AMP [11,13,14] . The effects of cyclic GMP act through phosphorylation of proteins by cyclic GMP-dependent protein kinase, direct inhibition on L-type calcium channels on cell membranes, decreasing calcium current and cyclic GMP-stimulated or cyclic GMP-inhibited cyclic AMP phosphodiesterases, which change the intracellular level of cyclic AMP [12,15,16] .…”

mentioning

confidence: 99%

“…Thus, cyclic AMP and cyclic GMP can interact through the cyclic GMP-affected cyclic AMP phosphodiesterases or at the level of their respective protein kinases. We have previously demonstrated interaction through cyclic GMP-induced changes in the level of cyclic AMP [11,13] . Cardiac hypertrophy develops as a basic response to persistent increases in blood pressure [17][18][19] .…”

mentioning

confidence: 99%

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Functional Interaction of a β-Adrenergic Agonist and Cyclic GMP Phosphodiesterase Inhibitor in Control and Hypertrophic Cardiomyocytes

Zhang

Rodríguez²,

Scholz³

et al. 2006

Pharmacology

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This study tested the hypothesis that the positive inotropic effect of β-adrenoceptor stimulation would be inhibited by increases in cyclic GMP in control cardiomyocytes and that this response would be modified in hypertrophic cardiomyocytes. Cell functional data as well as GMP and cyclic AMP data were collected from 7 control and 7 1K1C (one-kidney-one-clip) renal hypertensive hypertrophic rabbits. Using isolated control and IKIC ventricular myocytes, data were obtained at baseline and after treatment with the β-adrenoceptor agonist isoproterenol (10^{–8, –6} mol/l) or the cyclic GMP-phosphodiesterase inhibitor zaprinast (10^–5 mol/l) followed by isoproterenol (10^{–8, –6} mol/l). We found that in control rabbits, isoproterenol (10^–6 mol/l) increased percent shortening (4.8 ± 0.2 to 6.4 ± 0.3%) and cyclic AMP (2.3 ± 0.3 to 5.0 ± 0.7 pmol/10⁵ cells). Zaprinast 10^–5 mol/l increased cyclic GMP (150 ± 20 to 209 ± 14 fmol/10⁵ cells) and decreased percent shortening (6.2 ± 0.4 to 5.2 ± 0.3). Zaprinast 10^–5 mol/l prevented the functional response to isoproterenol in control (5.2 ± 0.3 to 4.7 ± 0.3), without changing cyclic AMP levels. In 1K1C rabbits, isoproterenol (10^–6 mol/l) increased cyclic AMP (4.9 ± 0.8 to 7.6 ± 1.4 pmol/10⁵ cells) without changing function. Zaprinast 10^–5 mol/l increased cyclic GMP (182 ± 23 to 233 ± 24 fmol/10⁵ cells) and decreased percent shortening (6.6 ± 0.9 to 4.7 ± 0.5), but did not alter the lack of effect of isoproterenol in 1K1C. In control cardiomyocytes, cyclic GMP blunted the isoproterenol contraction response without changing cyclic AMP levels, but isoproterenol’s functional effect was not seen in 1K1C cardiomyocytes.