Nitric Oxide Synthase Is the Mediator of Late Preconditioning Against Myocardial Infarction in Conscious Rabbits

Takano, Hitoshi; Manchikalapudi, Srinivas; Tang, Xian Liang; Qiu, Yumin; Rizvi, Ali A.; Jadoon, Asad K.; Zhang, Qin; Bolli, Roberto

doi:10.1161/01.cir.98.5.441

Cited by 229 publications

(254 citation statements)

References 71 publications

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“…On the one hand, anemia has been associated with higher mortality in cardiac patients and, by stimulating hematopoiesis, EPO may increase O 2 delivery to the myocardium, resulting in some functional benefit (24,29). On the other hand, correction of hematocrit may not translate into therapeutic gains.…”

Section: Discussionmentioning

confidence: 99%

“…In this protocol, rabbits underwent a 30-minute occlusion of the LCx followed by 3 days of reperfusion. Rabbits were randomly and blindly treated with EPO or saline at the time of reperfusion as described above, and 3 days later the LV ischemic area and infarcts were analyzed by standard TTC-pthalo blue staining (23,24). Notably, while the potential ischemic zone was similar in both MI groups (EPO: 32.1% ± 3.9%, n = 5; saline: 31.1% ± 4.0%, n = 5), the percentage of infarcted tissue in this area at risk was significantly reduced in the EPO group (13.8% ± 4.7%) as compared with the saline group (35.1% ± 4.3%, P = 0.004) (Figure 5a).…”

Section: Figurementioning

confidence: 99%

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A novel protective effect of erythropoietin in the infarcted heart

Parsa¹,

Matsumoto²,

Kim³

et al. 2003

J. Clin. Invest.

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Erythropoietin (EPO) has been shown to protect neurons from ischemic stroke, but can also increase thrombotic events and mortality rates in patients with ischemic heart disease. We reasoned that benefits of EPO might be offset by increases in hematocrit and evaluated the direct effects of EPO in the ischemic heart. We show that preconditioning with EPO protects H9c2 myoblasts in vitro and cardiomyocytes in vivo against ischemic injury. EPO treatment leads to significantly improved cardiac function following myocardial infarction. This protection is associated with mitigation of myocyte apoptosis, translating into more viable myocardium and less ventricular dysfunction. EPO-mediated myocyte survival appears to involve Akt activation. Importantly, cardioprotective effects of EPO were seen without an increase in hematocrit (eliminating oxygen delivery as an etiologic factor in myocyte survival and function), demonstrating that EPO can directly protect the ischemic and infarcted heart. Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: myocardial infarction (MI); erythropoietin (EPO); erythropoietin receptor (EPO-R); Janus-associated kinase-2 (Jak2); trichloroacetic acid (TCA); left circumflex coronary artery (LCx); reactive oxygen species (ROS); left ventricle (LV); triphenyltetrazolium chloride (TTC); β-adrenergic receptor (βAR); LV end-diastolic pressure (LVEDP).

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Section: Discussionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

A novel protective effect of erythropoietin in the infarcted heart

Parsa¹,

Matsumoto²,

Kim³

et al. 2003

J. Clin. Invest.

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“…Animal studies have shown that statins protect against ischemia-reperfusion injury and when administered before ischemia (2,5,7,31,32,46,48,49,54,55,59,62,63,68,69), or immediately upon reperfusion (4,18,62), limit myocardial infarct size (IS). The activation of eNOS is essential for the IS-limiting effects of late ischemic preconditioning (8,9,53,66). Similarly, several investigators have shown that the activation of Akt and endothelial NOS (eNOS) is essential for the myocardial protective effect of statins, since nonspecific NOS inhibitors blunt the IS-limiting effect of statins (5,63) and statins do not reduce IS in eNOS Ϫ/Ϫ mice (1,4,19,31,68,71).…”

mentioning

confidence: 99%

Pioglitazone protects the myocardium against ischemia-reperfusion injury in eNOS and iNOS knockout mice

Ye¹,

Lin²,

Manickavasagam³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Ye Y, Lin Y, Manickavasagam S, Perez-Polo JR, Tieu BC, Birnbaum Y. Pioglitazone protects the myocardium against ischemia-reperfusion injury in eNOS and iNOS knockout mice. Am J Physiol Heart Circ Physiol 295: H2436 -H2446, 2008. First published October 17, 2008 doi:10.1152/ajpheart.00690.2008.-Endothelial nitric oxide synthase (eNOS) activation with subsequent inducible NOS (iNOS), cytosolic phospholipase A2 (cPLA2), and cyclooxygenase-2 (COX2) activation is essential to statin inhibition of myocardial infarct size (IS). In the rat, the peroxisome proliferator-activated receptor-␥ agonist pioglitazone (Pio) limits IS, upregulates and activates cPLA 2 and COX2, and increases myocardial 6-keto-PGF1␣ levels without activating eNOS and iNOS. We asked whether Pio also limits IS in eNOS Ϫ/Ϫ and iNOS Ϫ/Ϫ mice. Male C57BL/6 wild-type (WT), eNOS Ϫ/Ϫ , and iNOS Ϫ/Ϫ mice received 10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 Pio (Pioϩ) or water alone (PioϪ) for 3 days. Mice underwent 30 min coronary artery occlusion and 4 h reperfusion, or hearts were harvested and subjected to ELISA and immunoblotting. As a result, Pio reduced IS in the WT (15.4 Ϯ 1.4% vs. 39.0 Ϯ 1.1%; P Ͻ 0.001), as well as in the eNOS Ϫ/Ϫ (32.0 Ϯ 1.6% vs. 44.2 Ϯ 1.9%; P Ͻ 0.001) and iNOS Ϫ/Ϫ (18.0 Ϯ 1.2% vs. 45.5 Ϯ 2.3%; P Ͻ 0.001) mice. The protective effect of Pio in eNOS Ϫ/Ϫ mice was smaller than in the WT (P Ͻ 0.001) and iNOS Ϫ/Ϫ (P Ͻ 0.001) mice. Pio increased myocardial Ser633 and Ser1177 phosphorylated eNOS levels in the WT and iNOS Ϫ/Ϫ mice. iNOS was undetectable in all six groups. Pio increased cPLA 2, COX2, and PGI2 synthase levels in the WT, as well as in the eNOS Ϫ/Ϫ and iNOS Ϫ/Ϫ , mice. Pio increased the myocardial 6-keto-PGF 1␣ levels and cPLA2 and COX2 activity in the WT, eNOS Ϫ/Ϫ , and iNOS Ϫ/Ϫ mice. In conclusion, the myocardial protective effect of Pio is iNOS independent and may be only partially dependent on eNOS. Because eNOS activity decreases with age, diabetes, and advanced atherosclerosis, this effect may be relevant in a clinical setting and should be further characterized. endothelial nitric oxide synthase; inducible nitric oxide synthase; peroxisome proliferator-activated receptor-␥ PROTECTION AGAINST ischemia-reperfusion injury may have a potential benefit in three distinct clinical situations: 1) limiting reperfusion injury in patients presenting with ST-elevation acute myocardial infarction before undergoing reperfusion therapy; 2) short-to intermediate-term treatment before elective procedures that may pose a risk for myocardial ischemia, such as cardiac or noncardiac surgery or percutaneous coronary interventions; and 3) long-term treatment in patients with established coronary artery disease to minimize the damage from an effort-induced ischemia or a potential future myocardial infarction. In the present study we studied whether the myocardial protection effects of intermediate-term pretreatment with pioglitazone (Pio) is dependent on nitric oxide (NO) synthases (NOSs), using a model that may be relevant to the second option mentioned above....

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“…Маркерами ишемического повреждения и посред-никами прекондиционирования служат белки тепло-вого шока, супероксиддисмутаза, каталаза, глутати-онпероксидаза, глюкозо-6-фосфатдегидрогеназа, креатинфосфокиназа и индуцибельная NO-синтаза, уровень которых отличается от нормы даже спустя сутки после реперфузии [66,107]. Сохранение этих изменений увеличивает толерантность тканей к по-следующему длительному ишемическому стрессу, обеспечивая лучшее переживание клеток в условиях сниженного обеспечения энергетическими субстра-тами и кислородом.…”

Section: Aadsorasunclassified

From the S.P. Botkin’s idea of “preexposure” to preconditioning phenomenon. Perspectives for use of phenomena of ischemic and pharmacological preconditioning

Zarubina

Викторовна²,

Shabanov

et al. 2016

Rev Clin Pharm Drug Ther

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The phenomenon of ischemic preconditioning based on the S.P. Botkin’s idea about defense effect of disturbing factors acting in small intensities is observed in the review. The modern literature data about main types of preconditioning exposure, triggers and mechanisms of ischemic preconditioning are reviewed. This phenomenon was supported in many experiments in vivo and in vitro on animals of different spices as well as in humans in clinical conditions. Ischemic preconditioning is qualified as transient positive changes in the organs and tissues produced by activation of rapid endogenous adoptive processes in them during the short period of subletal ischemia and reperfusion and which defend them from subsequent ischemic episodes. There are early and late ischemic preconditioning (the second window of defense). The first type of ischemic preconditioning belongs to classic type of preconditioning and is produced by the short ischemic episodes (3-5 min) and similar intervals of reperfusion. Ischemic preconditioning observed in a day or more after preconditioning stimuli is named as late preconditioning with genes expression, synthesis of heat shock proteins (HSP 72 in particular) and NO synthase as the basis mechanisms underlying of it. Administration of triggers like adenosine, forbol ether, bradykinine or glycerol derivatives into the blood or ischemic tissues produces defense action similar to ischemic preconditioning and qualified as pharmacological preconditioning. Preconditioning induced by pharmacological agents are more preference than short ischemic episodes. Antihypoxic effects of benzimidazol derivatives in both an acute hypoxia and hypoxic preconditioning are described in the article. Other perspectives of pharmacological preconditioning in practical use are also discussed.

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Nitric Oxide Synthase Is the Mediator of Late Preconditioning Against Myocardial Infarction in Conscious Rabbits

Cited by 229 publications

References 71 publications

A novel protective effect of erythropoietin in the infarcted heart

A novel protective effect of erythropoietin in the infarcted heart

Pioglitazone protects the myocardium against ischemia-reperfusion injury in eNOS and iNOS knockout mice

From the S.P. Botkin’s idea of “preexposure” to preconditioning phenomenon. Perspectives for use of phenomena of ischemic and pharmacological preconditioning

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