Negative metabolic and coronary flow effects of decreases in cAMP and increases in cGMP in control and renal hypertensive rabbit hearts

Rodríguez, Roberto; Molino, Bruno; Weiss, Harvey R.; Scholz, Peter

doi:10.1152/japplphysiol.01115.2003

Cited by 2 publications

(9 citation statements)

References 28 publications

(98 reference statements)

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“…Cyclic GMP acts through multiple different pathways to exert its negative functional and metabolic effects. These actions of cyclic GMP are mediated through changes in ion channels and cytosolic calcium levels, cyclic GMP-affected phosphodiesterases and protein phosphorylation [11,12] . One effect of cyclic GMP is that it inhibits L-type calcium channels [15,26] .…”

Section: Discussionmentioning

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: 97%

“…We found that in control rabbits, isoproterenol (10 -6 mol/l) increased percent shortening cyclic AMP signaling [10] . 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] .…”

mentioning

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%

“…The importance and actions of cyclic GMP in cardiac hypertrophy have been little studied, although increases in cyclic GMP levels have been reported in some types of pressure-load cardiac hypertrophy and failure [22,23] . This may or may not reduce the negative myocardial metabolic and functional responses to cyclic GMP in renal hypertensive (one-kidney-one-clip, 1K1C) rabbits [11,20,24] . The interactions between cyclic GMP and cyclic AMP in 1K1C cardiac hypertrophy have not been extensively studied.…”

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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.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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A Biphasic and Brain-Region Selective Down-Regulation of Cyclic Adenosine Monophosphate Concentrations Supports Object Recognition in the Rat

et al. 2012

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BackgroundWe aimed to further understand the relationship between cAMP concentration and mnesic performance.Methods and FindingsRats were injected with milrinone (PDE3 inhibitor, 0.3 mg/kg, i.p.), rolipram (PDE4 inhibitor, 0.3 mg/kg, i.p.) and/or the selective 5-HT4R agonist RS 67333 (1 mg/kg, i.p.) before testing in the object recognition paradigm. Cyclic AMP concentrations were measured in brain structures linked to episodic-like memory (i.e. hippocampus, prefrontal and perirhinal cortices) before or after either the sample or the testing phase. Except in the hippocampus of rolipram treated-rats, all treatment increased cAMP levels in each brain sub-region studied before the sample phase. After the sample phase, cAMP levels were significantly increased in hippocampus (1.8 fold), prefrontal (1.3 fold) and perirhinal (1.3 fold) cortices from controls rat while decreased in prefrontal cortex (∼0.83 to 0.62 fold) from drug-treated rats (except for milrinone+RS 67333 treatment). After the testing phase, cAMP concentrations were still increased in both the hippocampus (2.76 fold) and the perirhinal cortex (2.1 fold) from controls animals. Minor increase were reported in hippocampus and perirhinal cortex from both rolipram (respectively, 1.44 fold and 1.70 fold) and milrinone (respectively 1.46 fold and 1.56 fold)-treated rat. Following the paradigm, cAMP levels were significantly lower in the hippocampus, prefrontal and perirhinal cortices from drug-treated rat when compared to controls animals, however, only drug-treated rats spent longer time exploring the novel object during the testing phase (inter-phase interval of 4 h).ConclusionsOur results strongly suggest that a “pre-sample” early increase in cAMP levels followed by a specific lowering of cAMP concentrations in each brain sub-region linked to the object recognition paradigm support learning efficacy after a middle-term delay.

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Negative metabolic and coronary flow effects of decreases in cAMP and increases in cGMP in control and renal hypertensive rabbit hearts

Cited by 2 publications

References 28 publications

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

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

A Biphasic and Brain-Region Selective Down-Regulation of Cyclic Adenosine Monophosphate Concentrations Supports Object Recognition in the Rat

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