Selective Modulation of Inducible Nitric Oxide Synthase Isozyme in Myocardial Infarction

Wildhirt, Stephen M.; Suzuki, Hiroshi; Horstman, Damian J.; S, Weismüller; Dudek, R.; Akiyama, Koichiro; Reichart, Bruno

doi:10.1161/01.cir.96.5.1616

Cited by 76 publications

(53 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous reports have shown the expression of iNOS in the unstimulated cardiac tissue. 20,21 Pretreatment with DPCPX prevented the CCPA-induced increase in iNOS expression, suggesting that the selective activation of A 1 ARs indeed triggered the signaling pathway.…”

Section: No and Intracellular Signalingmentioning

confidence: 97%

Inducible Nitric Oxide Synthase Mediates Delayed Myocardial Protection Induced by Activation of Adenosine A ₁ Receptors

et al. 2000

View full text Add to dashboard Cite

Background-The mechanism of delayed preconditioning induced by activation of adenosine A 1 receptors (A 1 ARs) is not fully understood. We determined the role of inducible nitric oxide synthase (iNOS) in mediating adenosine-induced late cardioprotection using pharmacological inhibitors and iNOS gene-knockout mice. Methods and Results-Adult male mice were treated with saline or an A 1 AR agonist, 2-chloro-N 6 -cyclopentyladenosine (CCPA). Twenty-four hours later, the hearts were perfused in Langendorff mode and subjected to 30 minutes of global ischemia followed by 30 minutes of reperfusion. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.1 mg/kg IP) and S-methylisothiourea (SMT; 3 mg/kg IP) were used to block A 1 ARs and iNOS, respectively. Infarct size (IS) was measured by triphenyltetrazolium chloride staining, and iNOS expression was measured by Western blots. Myocardial IS was reduced from 24.0Ϯ3.2% in the saline group to 12.2Ϯ2.5% in CCPA-treated mice (PϽ0.05). The infarct-reducing effect of CCPA was abrogated by DPCPX (29.3Ϯ3.4%) and SMT (32.3Ϯ2.6%) and was absent in mice with targeted ablation of iNOS (23.9Ϯ1.6%). CCPA produced improvement in postischemic end-diastolic pressure, developed pressure, and rate-pressure product, which was also blocked by DPCPX and SMT. Increased iNOS protein expression observed in CCPA-treated hearts was diminished by DPCPX. Conclusions-Selective

show abstract

Section: No and Intracellular Signalingmentioning

confidence: 97%

Inducible Nitric Oxide Synthase Mediates Delayed Myocardial Protection Induced by Activation of Adenosine A ₁ Receptors

et al. 2000

View full text Add to dashboard Cite

show abstract

“…Furthermore, in the setting of brief ischemia followed by reperfusion, we are interested in whether the reduction in TTC-negative tissue observed in early reperfusion signifies genuine reduction of eventual infarct size following extended reperfusion. Because the stained myocardium consists of a complex mixture of necrotic and surviving myocytes in the early reperfusion, at that time the method of TTC staining has limitations in its accuracy for evaluation of cell necrosis (24); furthermore, inducible NO synthase (iNOS) induced by proinflammatory cytokines occurring during the late phase of postischemic infarction could increase infarct size (47)(48)(49).…”

mentioning

confidence: 99%

“…The beneficial effects were evidenced by decreased infarct size/mortality to some extent; however, NOaspirin appeared to exacerbate cardiac dysfunction: a significantly higher hypertrophy index occurred than in the control group (P Ͻ 0.05). We hypothesized that this is likely NO accumulation during the myocardial infarction due to the excessive supplement of NO released from the NO moiety plus a large amount of NO induced from endogenous iNOS, where a high concentration of NO is believed to be detrimental to cardiac tissue (8,44,48). Interestingly, Liang et al (22) demonstrated that L-arginine (a substrate for NO production) administered at different time points during ischemia-reperfusion exerted different effects on postischemic myocardial injury.…”

mentioning

confidence: 99%

Cardioprotective effects of nitric oxide-aspirin in myocardial ischemia-reperfused rats

Fu¹,

Wang²,

Chen³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Cardioprotective effects of nitric oxide-aspirin in myocardial ischemia-reperfused rats. Am J Physiol Heart Circ Physiol 293: H1545-H1552, 2007. First published May 25, 2007; doi:10.1152/ajpheart.00064.2007.-In this study, the cardioprotective effects of nitric oxide (NO)-aspirin, the nitroderivative of aspirin, were compared with those of aspirin in an anesthetized rat model of myocardial ischemia-reperfusion. Rats were given aspirin or NO-aspirin orally for 7 consecutive days preceding 25 min of myocardial ischemia followed by 48 h of reperfusion (MI/R). Treatment groups included vehicle (Tween 80), aspirin (30 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), and NO-aspirin (56 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ). NO-aspirin, compared with aspirin, displayed remarkable cardioprotection in rats subjected to MI/R as determined by the mortality rate and infarct size. Mortality rates for vehicle (n ϭ 23), aspirin (n ϭ 22), and NO-aspirin groups (n ϭ 22) were 34.8, 27.3, and 18.2%, respectively. Infarct size of the vehicle group was 44.5 Ϯ 2.7% of the left ventricle (LV). In contrast, infarct size of the LV decreased in the aspirin-and NOaspirin-pretreated groups, 36.7 Ϯ 1.8 and 22.9 Ϯ 4.3%, respectively (both P Ͻ 0.05 compared with vehicle group; P Ͻ 0.05, NO-aspirin vs. aspirin ). Moreover, NO-aspirin also improved ischemiareperfusion-induced myocardial contractile dysfunction on postischemic LV developed pressure. In addition, NO-aspirin downregulated inducible NO synthase (iNOS; 0.37-fold, P Ͻ 0.01) and cyclooxygenase-2 (COX-2; 0.61-fold, P Ͻ 0.05) gene expression compared with the vehicle group after 48 h of reperfusion. Treatment with N G -nitro-L-arginine methyl ester (L-NAME; 20 mg/kg), a nonselective NOS inhibitor, aggravated myocardial damage in terms of mortality and infarct size but attenuated effects when coadministered with NO-aspirin. L-NAME administration did not alter the increase in iNOS and COX-2 expression but did reverse the NO-aspirin-induced inhibition of expression of the two genes. The beneficial effects of NO-aspirin appeared to be derived largely from the NO moiety, which attenuated myocardial injury to limit infarct size and better recovery of LV function following ischemia and reperfusion. nitroaspirin; aspirin; cardioprotection; ischemia-reperfusion; infarct size ISCHEMIC MYOCARDIAL TISSUE will inevitably induce necrosis if blood flow is not restored immediately. Early reperfusion after coronary obstruction is well established to recover injured myocardium; nevertheless, reperfusion itself is believed to bring about additional cellular injury (25,30). During the last two decades, numerous studies have been done that focus on the roles of nitric oxide (NO) in the pathogenesis progress and pharmacological intervention of myocardial ischemia and reperfusion. Of them, exogenous NO donors may provide therapeutic benefit and are also a recent conceptual advance in the management of reperfusion damage (1,17,19,39). However, conventional NO donors (e.g., organic nitrates) frequently result in unwanted hemodynamic effects due to the ...

show abstract

“…4 NO produced by iNOS has been implicated in many pathophysiological states leading to myocardial dysfunction. [5][6][7] Chronic hypoxia modulates NO responses in different cell models, but the relationship between hypoxia and NOS regulation in cardiac tissue is not well understood, 8 and it has not yet been investigated in humans. McQuillan et al 9 found decreased NO production and eNOS expression in endothelial cells exposed to chronic hypoxia.…”

mentioning

confidence: 99%

Influence of Hypoxia on Nitric Oxide Synthase Activity and Gene Expression in Children With Congenital Heart Disease

et al. 2001

View full text Add to dashboard Cite

Background-Chronic hypoxia has been shown to modulate nitric oxide (NO) responses in different cell models, but the relationship between hypoxia and NO synthase (NOS) regulation in humans was not studied. We studied the relationship between endothelial and inducible NOS (eNOS and iNOS) activities and expression and chronic hypoxia in children with cyanotic and acyanotic congenital heart defects. Methods and Results-Right atrial tissue was excised from 18 patients during cardiac surgery. eNOS and iNOS activities were measured by conversion of L- [H 3 ]arginine to L-[H 3 ]citrulline. Gene expression of eNOS and iNOS was quantified by competitive reverse transcription-polymerase chain reaction. The eNOS activity and expression were significantly reduced in cyanotic hearts compared with acyanotic hearts: 0.38Ϯ0.14 versus 1.06Ϯ0.11 pmol · mg Ϫ1 · min

show abstract

Selective Modulation of Inducible Nitric Oxide Synthase Isozyme in Myocardial Infarction

Cited by 76 publications

References 33 publications

Inducible Nitric Oxide Synthase Mediates Delayed Myocardial Protection Induced by Activation of Adenosine A ₁ Receptors

Inducible Nitric Oxide Synthase Mediates Delayed Myocardial Protection Induced by Activation of Adenosine A ₁ Receptors

Cardioprotective effects of nitric oxide-aspirin in myocardial ischemia-reperfused rats

Influence of Hypoxia on Nitric Oxide Synthase Activity and Gene Expression in Children With Congenital Heart Disease

Contact Info

Product

Resources

About

Selective Modulation of Inducible Nitric Oxide Synthase Isozyme in Myocardial Infarction

Cited by 76 publications

References 33 publications

Inducible Nitric Oxide Synthase Mediates Delayed Myocardial Protection Induced by Activation of Adenosine A 1 Receptors

Inducible Nitric Oxide Synthase Mediates Delayed Myocardial Protection Induced by Activation of Adenosine A 1 Receptors

Cardioprotective effects of nitric oxide-aspirin in myocardial ischemia-reperfused rats

Influence of Hypoxia on Nitric Oxide Synthase Activity and Gene Expression in Children With Congenital Heart Disease

Contact Info

Product

Resources

About

Inducible Nitric Oxide Synthase Mediates Delayed Myocardial Protection Induced by Activation of Adenosine A ₁ Receptors

Inducible Nitric Oxide Synthase Mediates Delayed Myocardial Protection Induced by Activation of Adenosine A ₁ Receptors