Altered contractile response due to increased β3- adrenoceptor stimulation in diabetic cardiomyopathy: The role of nitric oxide synthase 1-derived nitric oxide

Julien Amour, Xavier Loyer, Morgan Le Guen, Nejma Mabrouk, Jean Stéphane David, Emmanuel Camors, Nunzia Carusio, Benoît Vivien, Ramaroson Andriantsitohaina, Christophe Heymes, Bruno Riou

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Abstract

BACKGROUND: In the diabetic heart, the positive inotropic response to β-adrenoceptor stimulation is altered and β1 and β2 adrenoceptors are down-regulated, whereas β3 adrenoceptor is up-regulated. In heart failure, β3-adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of β3-adrenoceptor in diabetic cardiomyopathy. METHODS: β-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of β3-adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline ± SD. RESULTS: The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 ± 15% vs. 160 ± 16%; P < 0.05) and in vitro (112 ± 5% vs. 179 ± 15%; P < 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of β3-adrenoceptor antagonist (174 ± 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 ± 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino- 3-butenyl)-l-ornithine [l-VNIO]; 172 ± 13%). In diabetes, in parallel with the increase in β3-adrenoceptor protein expression, the positive inotropic effect was partially restored by β3-adrenoceptor antagonist (137 ± 8%; P < 0.05), l-NAME (133 ± 11%; P < 0.05), or l-VNIO (130 ± 13%; P < 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable. CONCLUSIONS: β3-Adrenoceptor is involved in altered positive inotropic response to β-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic cardiomyocyte.

Original languageEnglish (US)
Pages (from-to)452-460
Number of pages9
JournalAnesthesiology
Volume107
Issue number3
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

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Diabetic Cardiomyopathies
Nitric Oxide Synthase
Adrenergic Receptors
Nitric Oxide
Cardiac Myocytes
Dobutamine
Papillary Muscles
Nitric Oxide Synthase Type III
Electron Spin Resonance Spectroscopy
Streptozocin
Adrenergic Agents
Arginine
Echocardiography
Proteins

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

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Altered contractile response due to increased β3- adrenoceptor stimulation in diabetic cardiomyopathy : The role of nitric oxide synthase 1-derived nitric oxide. / Amour, Julien; Loyer, Xavier; Le Guen, Morgan; Mabrouk, Nejma; David, Jean Stéphane; Camors, Emmanuel; Carusio, Nunzia; Vivien, Benoît; Andriantsitohaina, Ramaroson; Heymes, Christophe; Riou, Bruno.

In: Anesthesiology, Vol. 107, No. 3, 01.09.2007, p. 452-460.

Research output: Contribution to journalArticle

Amour, J, Loyer, X, Le Guen, M, Mabrouk, N, David, JS, Camors, E, Carusio, N, Vivien, B, Andriantsitohaina, R, Heymes, C & Riou, B 2007, 'Altered contractile response due to increased β3- adrenoceptor stimulation in diabetic cardiomyopathy: The role of nitric oxide synthase 1-derived nitric oxide', Anesthesiology, vol. 107, no. 3, pp. 452-460. https://doi.org/10.1097/01.anes.0000278909.40408.24
Amour, Julien ; Loyer, Xavier ; Le Guen, Morgan ; Mabrouk, Nejma ; David, Jean Stéphane ; Camors, Emmanuel ; Carusio, Nunzia ; Vivien, Benoît ; Andriantsitohaina, Ramaroson ; Heymes, Christophe ; Riou, Bruno. / Altered contractile response due to increased β3- adrenoceptor stimulation in diabetic cardiomyopathy : The role of nitric oxide synthase 1-derived nitric oxide. In: Anesthesiology. 2007 ; Vol. 107, No. 3. pp. 452-460.
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T1 - Altered contractile response due to increased β3- adrenoceptor stimulation in diabetic cardiomyopathy

T2 - The role of nitric oxide synthase 1-derived nitric oxide

AU - Amour, Julien

AU - Loyer, Xavier

AU - Le Guen, Morgan

AU - Mabrouk, Nejma

AU - David, Jean Stéphane

AU - Camors, Emmanuel

AU - Carusio, Nunzia

AU - Vivien, Benoît

AU - Andriantsitohaina, Ramaroson

AU - Heymes, Christophe

AU - Riou, Bruno

PY - 2007/9/1

Y1 - 2007/9/1

N2 - BACKGROUND: In the diabetic heart, the positive inotropic response to β-adrenoceptor stimulation is altered and β1 and β2 adrenoceptors are down-regulated, whereas β3 adrenoceptor is up-regulated. In heart failure, β3-adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of β3-adrenoceptor in diabetic cardiomyopathy. METHODS: β-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of β3-adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline ± SD. RESULTS: The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 ± 15% vs. 160 ± 16%; P < 0.05) and in vitro (112 ± 5% vs. 179 ± 15%; P < 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of β3-adrenoceptor antagonist (174 ± 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 ± 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino- 3-butenyl)-l-ornithine [l-VNIO]; 172 ± 13%). In diabetes, in parallel with the increase in β3-adrenoceptor protein expression, the positive inotropic effect was partially restored by β3-adrenoceptor antagonist (137 ± 8%; P < 0.05), l-NAME (133 ± 11%; P < 0.05), or l-VNIO (130 ± 13%; P < 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable. CONCLUSIONS: β3-Adrenoceptor is involved in altered positive inotropic response to β-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic cardiomyocyte.

AB - BACKGROUND: In the diabetic heart, the positive inotropic response to β-adrenoceptor stimulation is altered and β1 and β2 adrenoceptors are down-regulated, whereas β3 adrenoceptor is up-regulated. In heart failure, β3-adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of β3-adrenoceptor in diabetic cardiomyopathy. METHODS: β-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of β3-adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline ± SD. RESULTS: The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 ± 15% vs. 160 ± 16%; P < 0.05) and in vitro (112 ± 5% vs. 179 ± 15%; P < 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of β3-adrenoceptor antagonist (174 ± 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 ± 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino- 3-butenyl)-l-ornithine [l-VNIO]; 172 ± 13%). In diabetes, in parallel with the increase in β3-adrenoceptor protein expression, the positive inotropic effect was partially restored by β3-adrenoceptor antagonist (137 ± 8%; P < 0.05), l-NAME (133 ± 11%; P < 0.05), or l-VNIO (130 ± 13%; P < 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable. CONCLUSIONS: β3-Adrenoceptor is involved in altered positive inotropic response to β-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic cardiomyocyte.

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