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

Yan, Lin; Zhang, Qihang; Scholz, Peter; Weiss, Harvey R.

doi:10.1111/j.1440-1681.2003.03936.x

Cited by 12 publications

(14 citation statements)

References 36 publications

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“…Cyclic GMP has been shown to exert various inhibitory actions on cardiac myocytes including negative inotropic effects [15], reductions in metabolism [16] and inhibition of L-type calcium channels [17]. The level of this second messenger is increased by both nitric oxide and natriuretic peptides.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Inducible Factor-1 Protects Against Nitrate Tolerance and Stunning in Rabbit Cardiac Myocytes

Tan¹,

Weiss²

2010

Cardiovasc Drugs Ther

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Purpose We tested whether upregulation of hypoxia inducible factor-1 (HIF-1) would restore the blunted effects of natriuretic peptides and nitric oxide caused by chronic nitrate exposure and stunning in cardiac myocytes. Methods HIF-1α was increased with deferoxamine (150 mg/kg for 2 days). Nitrate tolerance was induced by a chronic nitroglycerin patch (0.3 mg/h for 5 days). We used freshly isolated rabbit ventricular myocytes. Half the myocytes were subjected to simulated ischemia [15 min 95% N 2 -5% CO 2 ] and reperfusion [reoxygenation] to produce stunning. Cell function was measured utilizing a video-edge detector. Shortening was examined at baseline and after brain natriuretic peptide (BNP, 10 −8 , 10 −7 M) or S-nitroso-N-acetyl-penicillamine (SNAP, 10 −6 , 10 −5 M) followed by KT5823 (cyclic GMP protein kinase inhibitor, 10 −6 M). We also measured cyclic GMP protein kinase protein levels and kinase activity. Results In control, BNP (−29%) reduced percent shortening, while KT5823 partially restored function. Deferoxamine treated control myocytes responded similarly. In patched nonstunned myocytes, BNP (−12%) reduced shortening less and KT5823 did not increase function. However, deferoxamine restored the blunted effects of BNP (−21%) and KT5823. In stunned myocytes, BNP (−11%) reduced shortening less and KT5823 did not affect function. Deferoxamine increased the effects of BNP (−27%) and KT5823 in stunning. Patch combined with stunning also similarly blunted the effects of BNP (−12%) and KT5823. Deferoxamine improved the effects of BNP (−22%) and KT5823. Similar results were observed after SNAP. Stunning reduced cyclic GMP protein kinase activity and deferoxamine restored activity. Deferoxamine had no effect on kinase activity in nitrate tolerance. Conclusion We found that upregulation of HIF-1 could protect isolated cardiac myocytes against nitrate tolerance through a cyclic GMP protein kinase-independent mechanism and through a kinase-dependent mechanism in stunning.

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Section: Discussionmentioning

confidence: 99%

Hypoxia Inducible Factor-1 Protects Against Nitrate Tolerance and Stunning in Rabbit Cardiac Myocytes

Tan¹,

Weiss²

2010

Cardiovasc Drugs Ther

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“…The effects of cyclic GMP were significantly blunted in the 1K1C cardiac myocytes. Previous studies had suggested reduced cyclic GMP-dependent protein kinase activity in this and other models of cardiac hypertrophy [5,16,17] . There may also be reductions in the activity of some of the cyclic GMP-affected cyclic AMP phosphodiesterases in myocardial hypertrophy [4] .…”

Section: Discussionmentioning

confidence: 99%

“…However, the reduced functional effects of cyclic GMP in 1K1C myocytes were still blocked by inhibition of SERCA. This suggested that other factors that cyclic GMP affects, such as changes in cyclic GMP protein kinase or cyclic GMP-affected cyclic AMP phosphodiesterases, were important [4,5,16,17] . It also suggested that the effects of cyclic GMP on phospholamban [20] , which have major effects on SER-CA activity, were not significantly altered in the 1K1C hypertrophic ventricular myocyte.…”

Section: Discussionmentioning

confidence: 99%

“…The functional responses to cyclic GMP tend to be reduced in hypertrophic myocytes. Cyclic GMP-dependent protein kinase activity is reduced in hypertrophic cardiac myocytes [5,17] . Since cyclic GMPinduced reductions in cardiac myocyte function are partially mediated by activation of the sarcoplasmic reticulum Ca 2+ -ATPase [8] , it is crucial to determine whether the importance of SERCA changes in hypertrophy.…”

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confidence: 99%

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SERCA Inhibition Limits the Functional Effects of Cyclic GMP in Both Control and Hypertrophic Cardiac Myocytes

et al. 2009

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The negative functional effects of cyclic GMP are controlled by the sarcoplasmic reticulum calcium-ATPase (SERCA). The effects of cyclic GMP are blunted in cardiac hypertrophy. We tested the hypothesis that the interaction between cyclic GMP and SERCA would be reduced in hypertrophic cardiac myocytes. Myocytes were isolated from 7 control and 7 renal-hypertensive hypertrophic rabbits. Control and hypertrophic myocytes received 8-bromo-cGMP (8-Br-cGMP; 10^–7, 10^–6, 10^–5 mol/l), the SERCA blocker thapsigargin (10^–8 mol/l) followed by 8-Br-cGMP, or the SERCA blocker, cyclopiazonic acid (CPA; 10^–7 mol/l) followed by 8-Br-cGMP. Percent shortening and maximal rate of shortening and relaxation were recorded using a video edge detector. Changes in cytosolic Ca²⁺ were assessed in fura 2-loaded myocytes. In controls, 8-Br-cGMP caused a significant 36% decrease in percent shortening from 5.8 ± 0.4 to 3.7 ± 0.3%. Thapsigargin and CPA did not affect basal control or hypertrophic myocyte function. When 8-Br-cGMP was given following thapsigargin or CPA, the negative effects of 8-Br-cGMP on control myocyte function were reduced. In hypertrophic myocytes, 8-Br-cGMP caused a smaller but significant 17% decrease in percent shortening from 4.7 ± 0.2 to 3.9 ± 0.1%. When 8-Br-cGMP was given following thapsigargin or CPA, no significant changes occurred in hypertrophic cell function. Intracellular Ca²⁺ transients responded in a similar manner to changes in cell function in control and hypertrophic myocytes. These results show that the effects of cyclic GMP were reduced in hypertrophic myocytes, but this was not related to SERCA. In presence of SERCA inhibitors, the responses to cyclic GMP were blunted in hypertrophic as well as control myocytes.

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“…There are many reports of depressed ␤ -adrenoceptor responses in pressure overload hypertrophy [17,20,21,28] . Some of this depressed effect has been ascribed to reduced ␤ -adrenoceptor levels or reduced adenylyl cyclase activity.…”

Section: Discussionmentioning

confidence: 99%

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.

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

Cited by 12 publications

References 36 publications

Hypoxia Inducible Factor-1 Protects Against Nitrate Tolerance and Stunning in Rabbit Cardiac Myocytes

Hypoxia Inducible Factor-1 Protects Against Nitrate Tolerance and Stunning in Rabbit Cardiac Myocytes

SERCA Inhibition Limits the Functional Effects of Cyclic GMP in Both Control and Hypertrophic Cardiac Myocytes

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

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