Cardiomyocyte-restricted restoration of nitric oxide synthase 3 attenuates left ventricular remodeling after chronic pressure overload

2007 ◽  
Vol 293 (1) ◽  
pp. H620-H627 ◽  
Author(s):  
Emmanuel S. Buys ◽  
Michael J. Raher ◽  
Sarah L. Blake ◽  
Tomas G. Neilan ◽  
Amanda R. Graveline ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Ventricular Remodeling ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Cardiac Response ◽  
Lv Remodeling ◽  
And Function ◽  
Oxide Synthase ◽  
Deficient Mice

Although nitric oxide synthase (NOS)3 is implicated as an important modulator of left ventricular (LV) remodeling, its role in the cardiac response to chronic pressure overload is controversial. We examined whether selective restoration of NOS3 to the hearts of NOS3-deficient mice would modulate the LV remodeling response to transverse aortic constriction (TAC). LV structure and function were compared at baseline and after TAC in NOS3-deficient (NOS3−/−) mice and NOS3−/− mice carrying a transgene directing NOS3 expression specifically in cardiomyocytes (NOS3−/−TG mice). At baseline, echocardiographic assessment of LV dimensions and function, invasive hemodynamic measurements, LV mass, and myocyte width did not differ between the two genotypes. Four weeks after TAC, echocardiographic and hemodynamic indexes of LV systolic function indicated that contractile performance was better preserved in NOS3−/−TG mice than in NOS3−/− mice. Echocardiographic LV wall thickness and cardiomyocyte width were greater in NOS3−/− mice than in NOS3−/−TG mice. TAC-induced cardiac fibrosis did not differ between these genotypes. TAC increased cardiac superoxide generation in NOS3−/−TG but not NOS3−/− mice. The ratio of NOS3 dimers to monomers did not differ before and after TAC in NOS3−/−TG mice. Restoration of NOS3 to the heart of NOS3-deficient mice attenuates LV hypertrophy and dysfunction after TAC, suggesting that NOS3 protects against the adverse LV remodeling induced by prolonged pressure overload.

scholarly journals Nitric oxide synthase 3 deficiency limits adverse ventricular remodeling after pressure overload in insulin resistance

2011 ◽  
Vol 301 (5) ◽  
pp. H2093-H2101 ◽  
Author(s):  
Baptiste Kurtz ◽  
Helene B. Thibault ◽  
Michael J. Raher ◽  
John R. Popovich ◽  
Sharon Cawley ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Insulin Resistance ◽  
Mitochondrial Respiration ◽  
Pressure Overload ◽  
Lv Remodeling ◽  
Stress Levels ◽  
Nitric Oxide Synthase 3 ◽  
And Function ◽  
Oxide Synthase

Insulin resistance (IR) and systemic hypertension are independently associated with heart failure. We reported previously that nitric oxide synthase 3 (NOS3) has a beneficial effect on left ventricular (LV) remodeling and function after pressure-overload in mice. The aim of our study was to investigate the interaction of IR and NOS3 in pressure-overload-induced LV remodeling and dysfunction. Wild-type (WT) and NOS3-deficient (NOS3−/−) mice were fed either a standard diet (SD) or a high-fat diet (HFD) to induce IR. After 9 days of diet, mice underwent transverse aortic constriction (TAC). LV structure and function were assessed serially using echocardiography. Cardiomyocytes were isolated, and levels of oxidative stress were evaluated using 2′,7′-dichlorodihydrofluorescein diacetate. Cardiac mitochondria were isolated, and mitochondrial respiration and ATP production were measured. TAC induced LV remodeling and dysfunction in all mice. The TAC-induced decrease in LV function was greater in SD-fed NOS3−/− mice than in SD-fed WT mice. In contrast, HFD-fed NOS3−/− developed less LV remodeling and dysfunction and had better survival than did HFD-fed WT mice. Seven days after TAC, oxidative stress levels were lower in cardiomyocytes from HFD-fed NOS3−/− than in those from HFD-fed WT. Nω-nitro-l-arginine methyl ester and mitochondrial inhibitors (rotenone and 2-thenoyltrifluoroacetone) decreased oxidative stress levels in cardiomyocytes from HFD-fed WT mice. Mitochondrial respiration was altered in NOS3−/− mice but did not worsen after HFD and TAC. In contrast with its protective role in SD, NOS3 increases LV adverse remodeling after pressure overload in HFD-fed, insulin resistant mice. Interactions between NOS3 and mitochondria may be responsible for increased oxidative stress levels in HFD-fed WT mice hearts.

Nitric oxide synthase 2 and pressure-overload-induced left ventricular remodelling in mice

2006 ◽  
Vol 91 (3) ◽  
pp. 633-639 ◽  
Author(s):  
Ryuji Hataishi ◽  
Ana Clara Rodrigues ◽  
John G. Morgan ◽  
Fumito Ichinose ◽  
Geneviève Derumeaux ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Ventricular Remodelling ◽  
Left Ventricular Remodelling ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase

scholarly journals Endothelial Nitric Oxide Synthase Limits Left Ventricular Remodeling After Myocardial Infarction in Mice

Circulation ◽  
2001 ◽  
Vol 104 (11) ◽  
pp. 1286-1291 ◽  
Author(s):  
Marielle Scherrer-Crosbie ◽  
Roman Ullrich ◽  
Kenneth D. Bloch ◽  
Hiroshi Nakajima ◽  
Boris Nasseri ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Myocardial Infarction ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Left ventricular adaptation to chronic pressure overload induced by inhibition of nitric oxide synthase in rats

1998 ◽  
Vol 93 (3) ◽  
pp. 173-181 ◽  
Author(s):  
B.B. Matsubara ◽  
L.S. Matsubara ◽  
L.A.M. Zornoff ◽  
M. Franco ◽  
J.S. Janicki
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Oxide Synthase

Effects of sex differences on constitutive nitric oxide synthase expression and activity in response to pressure overload in rats

2007 ◽  
Vol 293 (5) ◽  
pp. H2650-H2658 ◽  
Author(s):  
Xavier Loyer ◽  
Patricia Oliviero ◽  
Thibaud Damy ◽  
Estelle Robidel ◽  
Françoise Marotte ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sex Differences ◽  
Nitric Oxide Synthase ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Female Rats ◽  
Male Rats ◽  
Male And Female ◽  
Constitutive Nitric Oxide Synthase ◽  
Oxide Synthase

Clinical studies have documented sex differences in left ventricular (LV) hypertrophy patterns, but the mechanisms are so far poorly defined. This study aimed to determine whether 1) severe pressure overload altered expression and/or activity of cardiac constitutive nitric oxide synthase (NOS1 and NOS3) and 2) these changes were modulated according to sex. Analyses were performed 0.4–20 wk after thoracic aortic constriction (TAC) in male and female Wistar rats. Male rats with TAC exhibited early signs of cardiac dysfunction, as shown by echocardiographic and LV end-diastolic pressure measurements, whereas females with TAC exhibited higher LV hypertrophy (+96% vs. males at 20 wk; P < 0.05). After TAC, cardiac NOS1 expression was rapidly induced (0.4 wk) and stable afterward in males ( P < 0.05 vs. sham groups), whereas it was delayed in females. Accordingly, specific NOS1 activity was increased by 2 wk in male rats with TAC (+122%; P < 0.001 vs. sham groups) and only by 20 wk in females (+220%; P < 0.001 vs. sham groups). NOS1 activity was correlated with NOS1 level. Regarding cardiac NOS3, expression was unaffected by TAC, and the decrease in activity observed at early and late times in male and female rats with TAC, respectively, is shown to be related to NOS3 allosteric regulator caveolin-1 level. The data demonstrated a unique sex-dependent regulation of the constitutive NOSs in response to TAC in rats; such a difference might play a role in the sex-dependent adaptability of the heart in response to pressure overload.

scholarly journals 17β-Estradiol Regulates Constitutive Nitric Oxide Synthase Expression Differentially in the Myocardium in Response to Pressure Overload

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4579-4584 ◽  
Author(s):  
Xavier Loyer ◽  
Thibaud Damy ◽  
Zuzana Chvojkova ◽  
Estelle Robidel ◽  
Françoise Marotte ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Left Ventricular Hypertrophy ◽  
Cardiac Function ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Constitutive Nitric Oxide Synthase ◽  
Oxide Synthase ◽  
Expression And Activity

Estrogens [E(2)] exert direct and indirect effects that can modulate the development of cardiac disease. However, the precise mechanisms that are involved remain undefined. Our objective was to investigate whether E(2) affected the activity and expression of constitutive nitric oxide synthase (NOS) isoforms (NOS3 and NOS1) in cardiac hypertrophy induced by thoracic aortic constriction (TAC). Ovariectomized (Ovx) and nonovariectomized Wistar rats were subjected to TAC. Ovx animals received E(2) or placebo 3 wk after surgery for 11 wk. Afterward cardiac function and degree of left ventricular hypertrophy were assessed by echocardiography. NOS activity and expression were studied by biochemical techniques. TAC led to significant left ventricular hypertrophy (&gt;90%) irrespective of hormonal status. Cardiac performance declined more in TAC+Ovx (−20%, P &lt; 0.015) than in the two other TAC groups [TAC and TAC+Ovx+E(2)]. Total NOS activity decreased significantly in the Ovx groups. In response to TAC, total NOS activity increased whatever the E(2) status. Specific NOS3 activity dramatically decreased in the Ovx groups (−55%, P &lt; 0.009) and was unaltered by TAC. By using coimmunoprecipitation assays, we showed that NOS3/caveolin-1 complexes negatively regulated NOS3 activity as a function of E(2) status. On the other hand, NOS1 expression and activity were markedly increased in hypertrophied myocardium (P &lt; 0.003), irrespective of E(2) status. This study demonstrates a differential regulation of NOS expression and activity in response to pressure overload and E(2) status, the former being mainly involved in the induction of NOS1, whereas the latter regulated NOS3 activity and in turn cardiac function.

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