scholarly journals Defective Allele of the Neuronal Nitric Oxide Synthase Gene Increases Insulin Resistance During Acute Phase of Myocardial Infarction.

2021 ◽  
Author(s):  
Otávio T Nóbrega ◽  
Alessandra M. Campos-Staffico ◽  
Elayne Kelen Oliveira ◽  
Daniel B Munhoz ◽  
Filipe A. Moura ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Myocardial Infarction ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Nitric Oxide Synthase ◽  
Acute Phase ◽  
Neuronal Nitric Oxide Synthase ◽  
No Production ◽  
Defective Allele ◽  
Oxide Synthase

Abstract Background: glycemia disorders are a strong predictor of mortality in ST-Elevation Myocardial Infarction (STEMI) patients. Disruption in nitric oxide (NO) production is associated with insulin-resistant states. We evaluated whether NO production in carriers of a defective allele of the neuronal nitric oxide synthase (nNOS or NOS1), whose in vivo expression is reduced by up to 50%, might influence the insulin response during acute phase of STEMI. Methods and Results: Consecutive patients with STEMI (n = 354) underwent clinical evaluations and genotyping for the promoter variation rs41279104. Blood tests were performed at admission (D1) and after five days (D5) of in-hospital follow up, with the disposition index assessed in the period. Flow-mediated dilation (FMD) was assessed by reactive hyperemia on the 30th day. Homozygotes for the defective allele (A) showed lower glycemia and insulin sensitivity at D1 while showing the highest b-cells function and no changes in the circulating NO pool, what is compatible with hyperresponsive b-cells to counteract the inherent glucose-resistant state of AA patients. At D5, glycemic scores shifted to indicate greater insulin sensitivity among A homozygotes, paralleled by a slight yet poor increase in NO bioavailability than that among G carriers. All in all, defective homozygotes showed greater insulin resistance expressed by the disposition index at admission, which was compensated 5 days after STEMI even though FMD of A carriers was lower compared to G homozygotes. Conclusion: a defective nNOS allele seems to elicit endocrine adaptation and to associate with insulin resistance during the acute phase of STEMI.

scholarly journals Defective Allele of the Neuronal Nitric Oxide Synthase Gene Increases Insulin Resistance During Acute Phase of Myocardial Infarction

2021 ◽  
Vol Volume 14 ◽  
pp. 3669-3676
Author(s):  
Otávio T Nóbrega ◽  
Alessandra M Campos-Staffico ◽  
Elayne Kelen Oliveira ◽  
Daniel B Munhoz ◽  
Filipe A Moura ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Myocardial Infarction ◽  
Insulin Resistance ◽  
Nitric Oxide Synthase ◽  
Acute Phase ◽  
Neuronal Nitric Oxide Synthase ◽  
Defective Allele ◽  
Oxide Synthase

scholarly journals Role of Myocardial Neuronal Nitric Oxide Synthase–Derived Nitric Oxide in β-Adrenergic Hyporesponsiveness After Myocardial Infarction–Induced Heart Failure in Rat

Circulation ◽  
2004 ◽  
Vol 110 (16) ◽  
pp. 2368-2375 ◽  
Author(s):  
Jennifer K. Bendall ◽  
Thibaud Damy ◽  
Philippe Ratajczak ◽  
Xavier Loyer ◽  
Virginie Monceau ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Oxide Synthase

Increased neuronal nitric oxide synthase-derived NO production in the failing human heart

The Lancet ◽  
2004 ◽  
Vol 363 (9418) ◽  
pp. 1365-1367 ◽  
Author(s):  
Thibaud Damy ◽  
Philippe Ratajczak ◽  
Ajay M Shah ◽  
Emmanuel Camors ◽  
Isabelle Marty ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Human Heart ◽  
Neuronal Nitric Oxide Synthase ◽  
No Production ◽  
Oxide Synthase

Abstract 1333: Modulation Of Cardiac Beta-adrenergic Responsiveness By The Neuronal Nitric Oxide Synthase/Sarcolemmal Calcium Pump Complex

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Tamer M Mohamed ◽  
Delvac Oceandy ◽  
Nasser Alatwi ◽  
Florence Baudoin ◽  
Elizabeth J Cartwright ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Neonatal Rat ◽  
No Production ◽  
Adrenergic Stimulation ◽  
Rat Cardiomyocytes ◽  
Adrenergic Response ◽  
Oxide Synthase

The pivotal role of neuronal nitric oxide synthase (nNOS) in regulating cardiac function has only recently been unveiled. Notably, others have shown that responsiveness to β-adrenergic stimulation is dependent on nNOS activity. In a cellular model, we showed that the Ca 2+ /calmodulin-dependent nNOS activity is reduced by overexpression of isoform 4b of the plasma membrane Ca 2+ /Calmodulin-dependent Ca 2+ -pump (PMCA4b), which binds to nNOS. We demonstrated that PMCA4b overexpression in the heart reduced β-adrenergic responsiveness in vivo via an nNOS dependent mechanism (Oceandy et al, Circulation 2007). Here we investigated the cellular mechanisms of the regulation of the β-adrenergic response by PMCA4b. We used an adenoviral system to overexpress PMCA4b (PMCA4b cells) or LacZ (control, C) in neonatal rat cardiomyocytes. PMCA4b cells showed an 18±5% and 24±5% reduction in nitric oxide (DAF-FM fluorescence) and cGMP levels, respectively (n=6, p<0.05 each) compared to C demonstrating the regulation of NO production by the PMCA4b in this system. Since nNOS has been shown to regulate phospholamban (PLB) phosphorylation, we examined phosphorylation of PLB at Ser16. PMCA4b cells showed a significant increase in Ser16-PLB at baseline (66±17%, p<0.05) compared to C. As a result of increased baseline Ser16-PLB in PMCA4b cells, β-adrenergic stimulation of PMCA4b cells using 2μM isoproter-enol (IP) showed reduced relative induction in Ser16-PLB (23±10% vs. 78±19% in C; n=5, p<0.05). Further analysis in adult cardiomyocytes isolated from our PMCA4b transgenic mice (PMCA4b TG) demonstrated that PMCA4b TG showed 3-fold higher Ser16-PLB phosphorylation at baseline compared to wild type (WT) myocytes and the relative response following β-adrenergic stimulation was significantly reduced (1.2±0.2 fold induction after IP treatment in PMCA4b TG, vs. 3.1±0.7 in WT, n=5, p<0.05). Thus, PMCA4b regulates NO production from nNOS, which in turn modulates cGMP levels and PLB phosphorylation. These findings provide mechanistic insight into the regulation of the β-adrenergic response in the heart by PMCA4b and place this Ca 2+ -pump upstream of the recently described pathway linking nNOS and Ser16-PLB phosphorylation and downstream of the β-adrenergic receptor(s).

scholarly journals Deficiency of Neuronal Nitric Oxide Synthase Increases Mortality and Cardiac Remodeling After Myocardial Infarction

Circulation ◽  
2005 ◽  
Vol 112 (22) ◽  
pp. 3415-3422 ◽  
Author(s):  
Roberto M. Saraiva ◽  
Khalid M. Minhas ◽  
Shubha V.Y. Raju ◽  
Lili A. Barouch ◽  
Eleanor Pitz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Myocardial Infarction ◽  
Nitric Oxide Synthase ◽  
Cardiac Remodeling ◽  
Neuronal Nitric Oxide Synthase ◽  
Oxide Synthase
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