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/y98-073

Cited by 11 publications

(14 citation statements)

References 23 publications

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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%

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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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Section: Discussionmentioning

confidence: 99%

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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“…In contrast, MB acts through a reduction in intracellular cGMP . Because of its unique mechanism of action, MB has been investigated across different clinical scenarios involving treatment‐refractory hypotension associated with low SVR such as that occurring during and after cardiopulmonary bypass, sepsis, and liver transplantation [, ]. In liver transplantation, however, there is significant controversy concerning the role of NO in the protection of the liver graft and concerning the benefits of MB during orthotopic liver transplantation (OLT) .…”

Section: Introductionmentioning

confidence: 99%

The effect of methylene blue during orthotopic liver transplantation on post reperfusion syndrome and postoperative graft function

Fukazawa

Pretto

2010

J Hepato Biliary Pancreat

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“… 4,12,14 There is good evidence that the second messenger cGMP may work through a cGMP‐stimulated protein kinase 14 . It has also been demonstrated that alterations in cGMP can affect the level of cAMP in the heart and myocytes 11,32 . This may explain some of the reported increases in function with low doses of NO 4 .…”

Section: Discussionmentioning

confidence: 99%

“…The nitric oxide (NO)-cGMP signal transduction system reduces heart and cardiac myocyte function and metabolism. 4,10,11 It also causes vascular smooth muscle dilatation. 12,13 Nitric oxide primarily acts through increases in cGMP, which can affect myocyte calcium levels, the degree of protein phosphorylation and cAMP levels.…”

Section: Introductionmentioning

confidence: 99%

Ageing blunts the effects of nitric oxide on myocardial O₂ consumption

Weiss

Lazar²,

Tse

et al. 2002

Clin Exp Pharma Physio

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1. In the present study, we tested the hypothesis that the negative myocardial metabolic effects of nitric oxide (NO) were reduced in old hearts. 2. Studies were conducted in 17 young (approximately 6 months) and 18 old (> 36 months) New Zealand anaesthetized open-chest rabbits. Either vehicle or s-nitroso-N-acetylpenicillamine (SNAP; 10-4 mol/L; a NO donor) was applied to the epicardial surface of the left ventricle. Coronary blood flow (microspheres) and artero-venous (a-v) O2 difference (microspectrophotometry) were used to determine subepicardial (EPI) and subendocardial (ENDO) O2 consumption. Wall thickening was determined ultrasonically. Cyclic GMP and guanylyl cyclase activity were also determined. Myocardial a-v O2 difference, flow, O2 consumption and wall thickening were comparable in young and old hearts. 3. The EPI and ENDO O2 consumption of SNAP-treated young hearts decreased significantly (> 25%) compared with vehicle (saline). However, SNAP had no significant effects on the O2 consumption of old hearts. In addition, SNAP decreased the percentage wall thickening in young (from 18.0 +/- 1.7 to 13.4 +/- 1.6%), but not old (from 14.5 +/- 0.9 to 11.4 +/- 1.6%), hearts. Basal cGMP levels in old hearts were greater (approximately 70%) than those in young hearts (15.7 +/- 2.0 vs 9.0 +/- 0.8 pmol/g, EPI). s-Nitroso-N-acetylpenicillamine increased cGMP in EPI (13.7 +/- 1.8 pmol/g) and ENDO of young, but not old (18.7 +/- 2.3 pmol/g, EPI), hearts. Similar results were also obtained using another NO donor, namely sodium nitroprusside (SNP; 10-4 mol/L). Guanylyl cyclase activity was elevated in old rabbit hearts with 0.5 mmol/L SNP (131 +/- 12 vs 80 +/- 12 pmol/min per mg protein for old and young rabbits, respectively). 4. Thus, while older hearts had similar O2 consumption and wall thickening compared with young hearts, they responded less well to NO and had significantly elevated basal levels of myocardial cGMP.

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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 23 publications

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

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

The effect of methylene blue during orthotopic liver transplantation on post reperfusion syndrome and postoperative graft function

Ageing blunts the effects of nitric oxide on myocardial O₂ consumption

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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 23 publications

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

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

The effect of methylene blue during orthotopic liver transplantation on post reperfusion syndrome and postoperative graft function

Ageing blunts the effects of nitric oxide on myocardial O2 consumption

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Ageing blunts the effects of nitric oxide on myocardial O₂ consumption