Brain natriuretic peptide limits myocardial infarct size dependent of nitric oxide synthase in rats

2007 ◽  
Vol 377 (1-2) ◽  
pp. 83-87 ◽  
Author(s):  
Binhui Ren ◽  
Yi Shen ◽  
Hongtao Shao ◽  
Jianjun Qian ◽  
Haiwei Wu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Brain Natriuretic Peptide ◽  
Infarct Size ◽  
Natriuretic Peptide ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Size Dependent ◽  
Oxide Synthase

Pharmacological inhibition of PTEN limits myocardial infarct size and improves left ventricular function postinfarction

2010 ◽  
Vol 298 (4) ◽  
pp. H1198-H1208 ◽  
Author(s):  
Kyle T. Keyes ◽  
Jing Xu ◽  
Bo Long ◽  
Congfang Zhang ◽  
Zhaoyong Hu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Left Ventricular Function ◽  
Infarct Size ◽  
Caspase 3 ◽  
Myocardial Infarct ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Pharmacological Inhibition ◽  
Oxide Synthase

Phosphoinositide 3-kinase (PI3K) mediates myocardium protective signaling through phosphorylation of phosphatidylinositol (Ptdins) to produce Ptdins(3,4,5)P3. Lipid phosphatase and tensin homolog on chromosome 10 (PTEN) antagonizes PI3K activity by dephosphorylating Ptdins(3,4,5)P3; therefore, the inhibition of PTEN enhances PI3K/Akt signaling and could prevent myocardium from ischemia-reperfusion (I/R) injury. Here we studied 1) whether the pharmacological inhibition of PTEN by bisperoxovanadium molecules [BpV(HOpic)] attenuates simulated I/R (SIR) injury in vitro and 2) whether the administration of BpV(HOpic) either before or after ischemia limits myocardial infarct size (IS) and ameliorates cardiodysfunction caused by infarction. First, adult rat cardiomyocytes were treated with or without BpV(HOpic) and then exposure to SIR. Second, anesthetized rats received BpV(HOpic) either before or after ischemia. IS was assessed at 4 h reperfusion, and left ventricular function was evaluated by echocardiography at 28 days postreperfusion. As a result, BpV(HOpic) decreased cell death, improved 3-[4,5-yl]-2,5-diphenyltetrazolium bromide (MTT) viability, and reduced apoptosis in cells exposed to SIR. These protective effects of BpV(HOpic) are associated with increased phospho-Akt and the repression of caspase-3 activity. Second, the administration of BpV(HOpic) significantly reduced IS and suppressed caspase-3 activity following I/R injury and consequentially improved cardiac function at 28 day postinfarction. These beneficial effects of BpV(HOpic) are attributed to increases in myocardial levels of phosphorylation of Akt/endothelial nitric oxide synthase (eNOS), ERK-1/2, and calcium-dependent nitric oxide synthase activity. In conclusion, the pharmacological inhibition of PTEN protects against I/R injury through the upregulation of the PI3K/Akt/eNOS/ERK prosurvival pathway, suggesting a new therapeutic strategy to combat I/R injury.

Desflurane-induced Preconditioning against Myocardial Infarction Is Mediated by Nitric Oxide

2006 ◽  
Vol 105 (4) ◽  
pp. 719-725 ◽  
Author(s):  
Thorsten M. Smul ◽  
Markus Lange ◽  
Andreas Redel ◽  
Natalie Burkhard ◽  
Norbert Roewer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Nitric Oxide Synthase Activity

Background Volatile anesthetics induce myocardial preconditioning through a signal transduction pathway that is remarkably similar to that observed during ischemic preconditioning. Nitric oxide-dependent signaling plays an important role in anesthetic and ischemic preconditioning. Therefore, the authors tested the hypothesis that desflurane-induced preconditioning is mediated by nitric oxide. Methods Barbiturate-anesthetized rabbits were instrumented for measurement of hemodynamics. All rabbits were subjected to 30-min coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size was assessed with triphenyltetrazolium chloride staining. Myocardial nitric oxide synthase activity was assessed with a [H]L-arginine-conversion assay. Rabbits were randomized to five separate experimental groups. They received 0.0 or 1.0 minimum alveolar concentration desflurane for 30 min, which was discontinued 30 min before ischemia in the absence or presence of the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA). L-NA was given either 20 min before or 10 min after desflurane administration, respectively. Data are mean +/- SEM. Results Infarct size was 56 +/- 8% in control experiments. Desflurane significantly (P < 0.05) reduced infarct size to 35 +/- 4%. Preconditioning by desflurane was totally blocked by administration of L-NA either during or after desflurane inhalation (58 +/- 4 and 59 +/- 9%, respectively). L-NA alone had no effect on infarct size (56 +/- 7%). Nitric oxide synthase activity was significantly (P < 0.05) increased by desflurane. Conclusion The results demonstrate that desflurane-induced preconditioning markedly reduced myocardial infarct size. This beneficial effect was blocked by the nitric oxide synthase inhibitor L-NA either during or after desflurane-administration. These data suggest that early desflurane-induced preconditioning is mediated by nitric oxide.

Relationship between Plasma Level of Brain Natriuretic Peptide and Myocardial Infarct Size

Cardiology ◽  
1994 ◽  
Vol 85 (5) ◽  
pp. 334-340 ◽  
Author(s):  
Naoshi Arakawa ◽  
Motoyuki Nakamura ◽  
Hidehiko Aoki ◽  
Katsuhiko Hiramori
Keyword(s):  
Plasma Level ◽  
Brain Natriuretic Peptide ◽  
Infarct Size ◽  
Natriuretic Peptide ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size

Endothelial nitric oxide synthase (NOS3) knockout decreases NOS2 induction, limiting hyperoxygenation and conferring protection in the postischemic heart

2007 ◽  
Vol 292 (3) ◽  
pp. H1541-H1550 ◽  
Author(s):  
Xue Zhao ◽  
Yeong-Renn Chen ◽  
Guanglong He ◽  
Aiwen Zhang ◽  
Lawrence J. Druhan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Infarct Size ◽  
Endothelial Nitric Oxide Synthase ◽  
Nadh Dehydrogenase ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Postischemic Myocardium ◽  
Inos Induction

Although it has been shown that endothelial nitric oxide synthase (eNOS)-derived nitric oxide downregulates mitochondrial oxygen consumption during early reperfusion, its effects on inducible NOS (iNOS) induction and myocardial injury during late reperfusion are unknown. Wild-type (WT) and eNOS−/− mice were subjected to 30 min of coronary ligation followed by reperfusion. Expression of iNOS mRNA and protein levels and peroxynitrite production were lower in postischemic myocardium of eNOS−/− mice than levels in WT mice 48 h postreperfusion. Significantly improved hemodynamics (±dP/d t, left ventricular systolic pressure, mean arterial pressure), increased rate pressure product, and reduced myocardial infarct size (18 ± 2.5% vs. 31 ± 4.6%) were found 48 h after reperfusion in eNOS−/− mice compared with WT mice. Myocardial infarct size was also significantly decreased in WT mice treated with the specific iNOS inhibitor 1400W (20.5 ± 3.4%) compared with WT mice treated with PBS (33.9 ± 5.3%). A marked reperfusion-induced hyperoxygenation state was observed by electron paramagnetic resonance oximetry in postischemic myocardium, but Po2 values were significantly lower from 1 to 72 h in eNOS−/− than in WT mice. Cytochrome c-oxidase activity and NADH dehydrogenase activity were significantly decreased in postischemic myocardium in WT and eNOS−/− mice compared with baseline control, respectively, and NADH dehydrogenase activity was significantly higher in eNOS−/− than in WT mice. Thus deficiency of eNOS exerted a sustained beneficial effect on postischemic myocardium 48 h after reperfusion with preserved mitochondrial function, which appears to be due to decreased iNOS induction and decreased iNOS-derived peroxynitrite in postischemic myocardium.

Myocardial ischemia-reperfusion injury is exacerbated in absence of endothelial cell nitric oxide synthase

1999 ◽  
Vol 276 (5) ◽  
pp. H1567-H1573 ◽  
Author(s):  
Steven P. Jones ◽  
Wesley G. Girod ◽  
Anthony J. Palazzo ◽  
D. Neil Granger ◽  
Matthew B. Grisham ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Nitric Oxide Synthase ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Polymorphonuclear Neutrophil ◽  
Myocardial Infarct Size ◽  
Wild Type ◽  
Myocardial Ischemia And Reperfusion ◽  
Oxide Synthase

Myocardial ischemia and reperfusion (MI/R) initiates a cascade of polymorphonuclear neutrophil (PMN)-mediated injury, the magnitude of which may be influenced by the bioavailability of nitric oxide (NO). We investigated the role of endothelial cell nitric oxide synthase (ecNOS) in MI/R injury by subjecting wild-type and ecNOS-deficient (−/−) mice to 20 min of coronary artery occlusion and 120 min of reperfusion. Myocardial infarct size represented 20.9 ± 2.9% of the ischemic zone in wild-type mice, whereas the ecNOS −/− mice had significantly ( P < 0.01) larger infarcts measuring 46.0 ± 3.8% of the ischemic zone. Because P-selectin is thought to be involved with the pathogenesis of neutrophil-mediated I/R injury, we assessed the effects of MI/R on P-selectin expression in the myocardium of wild-type and ecNOS −/− mice. P-selectin expression measured with a radiolabeled monoclonal antibody (MAb) technique after MI/R in wild-type mice was 0.037 ± 0.009 μg MAb/g tissue, whereas ecNOS −/− coronary vasculature was characterized by significantly ( P < 0.05) higher P-selectin expression (0.080 ± 0.013 μg MAb/g tissue). Histological examination of the postischemic myocardium revealed significantly ( P < 0.01) more neutrophils in the ecNOS −/− (29.5 ± 2.5 PMN/field) compared with wild-type (5.0 ± 0.9 PMN/field) mice. A similar trend in infarct size and neutrophil accumulation was observed when wild-type and ecNOS −/− mice were subjected to 30 min of ischemia and 120 min of reperfusion. These novel in vivo findings demonstrate a cardioprotective role for ecNOS-derived NO in the ischemic-reperfused mouse heart.

scholarly journals Isoflurane Favorably Modulates Guanosine Triphosphate Cyclohydrolase-1 and Endothelial Nitric Oxide Synthase during Myocardial Ischemia and Reperfusion Injury in Rats

2015 ◽  
Vol 123 (3) ◽  
pp. 582-589 ◽  
Author(s):  
Ines Baotic ◽  
Dorothee Weihrauch ◽  
Jesse Procknow ◽  
Jeanette Vasquez-Vivar ◽  
Zhi-Dong Ge ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Infarct Size ◽  
Endothelial Nitric Oxide Synthase ◽  
Myocardial Infarct ◽  
No Production ◽  
Myocardial Infarct Size ◽  
Ischemia And Reperfusion ◽  
Ischemia And Reperfusion Injury ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Abstract Background: The authors investigated the hypothesis that isoflurane modulates nitric oxide (NO) synthesis and protection against myocardial infarction through time-dependent changes in expression of key NO regulatory proteins, guanosine triphosphate cyclohydrolase (GTPCH)-1, the rate-limiting enzyme involved in the biosynthesis of tetrahydrobiopterin and endothelial nitric oxide synthase (eNOS). Methods: Myocardial infarct size, NO production (ozone-mediated chemiluminescence), GTPCH-1, and eNOS expression (real-time reverse transcriptase polymerase chain reaction and western blotting) were measured in male Wistar rats with or without anesthetic preconditioning (APC; 1.0 minimum alveolar concentration isoflurane for 30 min) and in the presence or absence of an inhibitor of GTPCH-1, 2,4-diamino-6-hydroxypyrimidine. Results: NO−2 production (158 ± 16 and 150 ± 13 pmol/mg protein at baseline in control and APC groups, respectively) was significantly (P &lt; 0.05) increased 1.5 ± 0.1 and 1.4 ± 0.1 fold by APC (n = 4) at 60 and 90 min of reperfusion, respectively, concomitantly, with increased expression of GTPCH-1 (1.3 ± 0.3 fold; n = 5) and eNOS (1.3 ± 0.2 fold; n = 5). In contrast, total NO (NO−2 and NO−3) was decreased after reperfusion in control experiments. Myocardial infarct size was decreased (43 ± 2% of the area at risk for infarction; n = 6) by APC compared with control experiments (57 ± 1%; n = 6). 2, 4-Diamino-6-hydroxypyrimidine decreased total NO production at baseline (221 ± 25 and 175 ± 31 pmol/mg protein at baseline in control and APC groups, respectively), abolished isoflurane-induced increases in NO at reperfusion, and prevented reductions of myocardial infarct size by APC (60 ± 2%; n = 6). Conclusion: APC favorably modulated a NO biosynthetic pathway by up-regulating GTPCH-1 and eNOS, and this action contributed to protection of myocardium against ischemia and reperfusion injury.

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