Positive inotropy due to lowering cyclic GMP is also mediated by increases in cyclic AMP in control and hypertrophic hearts

Naim, Karen L.; Rabindranauth, Prem; Weiss, Harvey R.; Tse, James; Leone, Richard J.; Scholz, Peter

doi:10.1139/cjpp-76-6-605

Cited by 11 publications

(13 citation statements)

References 24 publications

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“…Similar to our prior studies [28], the hypertrophied hearts responded to guanylate cyclase inhibition by increasing function and metabolism. We have shown that hypertrophied animals have elevated basal cyclic GMP levels per gram myocardial tissue and are capable of reducing cyclic GMP levels by inhibiting guanylate cyclase.…”

Section: Figsupporting

confidence: 79%

Pacing-Induced Cardiac Failure of Hypertrophic Hearts: Effects of Cyclic GMP Reduction

Huang¹,

Weiss²,

Tse³

et al. 1999

Journal of Surgical Research

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Section: Figsupporting

confidence: 79%

Pacing-Induced Cardiac Failure of Hypertrophic Hearts: Effects of Cyclic GMP Reduction

Huang¹,

Weiss²,

Tse³

et al. 1999

Journal of Surgical Research

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“…Previous work has demonstrated that the effects of cGMP are not changed by the activity of L‐type calcium channels in cardiac myocytes, 18,25 although calcium currents could be altered 26 . Cyclic GMP also antagonizes the positive inotropic effects of catecholamines and cAMP 12,13,27 . Cyclic GMP can change cAMP levels through cGMP‐regulated cAMP phosphodiesterases 12 .…”

Section: Discussionmentioning

confidence: 99%

“…Other studies have shown that blocking this pathway significantly diminishes the effects of cGMP 6,7,9–11 . Cyclic GMP also interacts with the second messenger cAMP through cGMP‐regulated cAMP phosphodiesterases 1,12 . However, these two second messengers can also interact at the level of their respective protein kinases 1,10 , 11,13 .…”

Section: Introductionmentioning

confidence: 99%

Cyclic GMP protein kinase activity is reduced in thyroxine‐induced hypertrophic cardiac myocytes

Yan

Zhang

Scholz

et al. 2003

Clin Exp Pharma Physio

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1. We tested the hypothesis that the cGMP-dependent protein kinase has major negative functional effects in cardiac myocytes and that the importance of this pathway is reduced in thyroxine (T4; 0.5 mg/kg per day for 16 days) hypertrophic myocytes. 2. Using isolated ventricular myocytes from control (n = 7) and T4-treated (n = 9) rabbit hypertrophic hearts, myocyte shortening was studied with a video edge detector. Oxygen consumption was measured using O2 electrodes. Protein phosphorylation was measured autoradiographically. 3. Data were collected following treatment with: (i) 8-(4-chlorophenylthio)guanosine-3',5'-monophosphate (PCPT; 10-7 or 10-5 mol/L); (ii) 8-bromo-cAMP (10-5 mol/L) followed by PCPT; (iii) beta-phenyl-1,N2-etheno-8-bromoguanosine-3',5'-monophosphorothioate, SP-isomer (SP; 10-7 or 10-5 mol/L); or (iv) 8-bromo-cAMP (10-5 mol/L) followed by SP. 4. There were no significant differences between groups in baseline percentage shortening (Pcs; 4.9 +/- 0.2 vs 5.6 +/- 0.4% for control and T4 groups, respectively) and maximal rate of shortening (Rs; 64.8 +/- 5.9 vs 79.9 +/- 7.1 micro m/ s for control and T4 groups, respectively). Both SP and PCPT decreased Pcs (-43 vs-21% for control and T4 groups, respectively) and Rs (-36 vs-22% for control and T4 groups, respectively), but the effect was significantly reduced in T4 myocytes. 8-Bromo-cAMP similarly increased Pcs (28 vs 23% for control and T4 groups, respectively) and Rs (20 vs 19% for control and T4 groups, respectively). After 8-bromo-cAMP, SP and PCPT decreased Pcs (-34%) and Rs (-29%) less in the control group. However, the effects of these drugs were not altered in T4 myocytes (Pcs -24%; Rs -22%). Both PCPT and cAMP phosphorylated the same five protein bands. In T4 myocytes, these five bands were enhanced less. 5. We conclude that, in control ventricular myocytes, the cGMP-dependent protein kinase exerted major negative functional effects but, in T4-induced hypertrophic myocytes, the importance of this pathway was reduced and the interaction between cAMP and the cGMP protein kinase was diminished.

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“…There are few studies on the importance of cGMP‐affected cAMP phosphodiesterases in the functional effects of cGMP. However, it has been demonstrated that alterations in cGMP can affect the level of cAMP in the heart and myocytes ( Muller et al , 1990 ; Mery et al , 1993 ; Joe et al , 1998 ; Naim et al , 1998 ). These studies demonstrated that cGMP could affect the level of cAMP through its effects on the cGMP‐stimulated and cGMP‐inhibited cAMP phosphodiesterases.…”

Section: Discussionmentioning

confidence: 99%

Opposing functional effects of cyclic GMP and cyclic AMP may act through protein phosphorylation in rabbit cardiac myocytes

Yan

Lee²,

Huang

et al. 2000

J. Autonom. Pharmacol.

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1. We tested the hypothesis that the negative functional effects of cyclic GMP (cGMP) oppose the positive effects of cyclic AMP (cAMP) in cardiac myocytes through interaction at the level of their respective protein kinases. 2. Cell shortening was studied using a video-edge detector. The O2 consumption of a suspension of rabbit ventricular myocytes was measured using O2 electrodes. Protein phosphorylation was measured autoradiographically following SDS-PAGE. Data were collected with: (1) 8-bromo-cGMP (8-Br-cGMP) 10(-7) or 10(-5) M; (2) 8-bromo-cAMP (8-Br-cAMP) 10(-7) or 10(-5) M; (3) 8-Br-cAMP 10(-5) M followed by 8-Br-cGMP 10(-7) or 10(-5) M; (4) 8-Br-cGMP 10(-5) M followed by 8-Br-cAMP 10(-7) or 10(-5) M; (5) 8-Br-cGMP 10(-7) or 10(-5) M followed by KT 5720 (cAMP-dependent protein kinase inhibitor) or KT 5823 (cGMP-dependent protein kinase inhibitor) 10(-6) M; and (6) 8-Br-cAMP 10(-7) or 10(-5) M followed by KT 5720 or KT 5823 10(-6) M. 3. 8-Br-cGMP 10(-5) M decreased percent shortening (Pcs) from 6.3+/-0.6 to 3.6+/-0.4% and rate of shortening (Rs) from 66.7+/-4.4 to 41.8+/-4.2 microm s(-1). 8-Br-cAMP 10(-5) M increased Pcs (from 3.7+/-0.2 to 4.8+/-0.2) and Rs (from 50.0+/-3.0 to 60.0+/-3.1). With 8-Br-cAMP 10(-5) M, 8-Br-cGMP 10(-5) M decreased Pcs and Rs less. The positive functional effects of 8-Br-cAMP 10(-7) or 10(-5) M were also diminished with 8-Br-cGMP 10(-5) M. Following 8-Br-cGMP 10(-7) or 10(-5) M, KT 5720 10(-6) M further decreased Pcs to 2.5+/-0.3 and Rs to 30.0+/-4.1. KT 5823 10(-6) M returned Pcs to 4.7+/-0.4 and Rs to 61.3+/-5.3. Following 8-Br-cAMP 10(-7) or 10(-5) M, KT 5720 decreased the elevated Pcs and Rs significantly and KT 5823 10(-6) M further increased these parameters. 4. cGMP and cAMP phosphorylated the same five protein bands. With KT 5720 or KT 5823, all of the bands were lighter at the same concentration of 8-Br-cAMP and 8-Br-cGMP. 5. We conclude that, in rabbit ventricular myocytes, the opposing functional effects of cGMP and cAMP are related to the interaction at the level of their respective protein kinases.

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Positive inotropy due to lowering cyclic GMP is also mediated by increases in cyclic AMP in control and hypertrophic hearts

Cited by 11 publications

References 24 publications

Pacing-Induced Cardiac Failure of Hypertrophic Hearts: Effects of Cyclic GMP Reduction

Pacing-Induced Cardiac Failure of Hypertrophic Hearts: Effects of Cyclic GMP Reduction

Cyclic GMP protein kinase activity is reduced in thyroxine‐induced hypertrophic cardiac myocytes

Opposing functional effects of cyclic GMP and cyclic AMP may act through protein phosphorylation in rabbit cardiac myocytes

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