Exercise improves the dilatation function of mesenteric arteries in postmyocardial infarction rats via a PI3K/Akt/eNOS pathway-mediated mechanism

Wang, Youhua; Wang, Shengpeng; Wier, W. Gil; Zhang, Quan‐Jiang; Jiang, Hong-Ke; Li, Qiuxia; Chen, Shengfeng; Tian, Zhenjun; Li, Youyou; Yu, Xin; Zhao, Ming; Liu, Jinjun; Yang, Jing; Zhang, Jing; Zang, Wei-Jin

doi:10.1152/ajpheart.00701.2010

Cited by 48 publications

(63 citation statements)

References 56 publications

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“…Immunohistochemical detection of eNOS was performed as previously described. 23 The arterial sections were incubated with blocking solutions (5% bovine serum albumin) and then with rabbit anti-eNOS antibody (1:200 dilution; Cell Signaling Technology, Beverly, MA, USA) overnight at 4 1C. The sections were then washed with phosphate-buffered saline (PBS; three times for 2 min each) and incubated at 37 1C in biotin-conjugated goat antirabbit immunoglobulin for 30 min.…”

Section: Hematoxylin and Eosin Staining And Immunohistochemistrymentioning

confidence: 99%

Delayed preconditioning prevents ischemia/reperfusion-induced endothelial injury in rats: role of ROS and eNOS

Zhao

et al. 2013

Laboratory Investigation

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Ischemic preconditioning (IPC) strongly protects against ischemia/reperfusion (I/R) injury; however, the molecular mechanism involved in delayed preconditioning-induced endothelial protection in peripheral arteries is unknown. Therefore, we examined using functional, morphologic and molecular biologic studies whether delayed IPC decreases formation of reactive oxygen species and upregulates endothelial nitric oxide synthase (eNOS) that in turn contributes to vascular endothelial protection. Adult male Sprague-Dawley rats were subjected to 30-min ischemia induced by mesenteric artery occlusion followed by 60-min reperfusion 24 h after sham surgery or preconditioning (three cycles of 5-min ischemia/5-min reperfusion). Delayed preconditioning prevented the I/R-induced impairment of endothelium-dependent relaxations to acetylcholine (maximal relaxation: sham 91.4 ± 2.2%; I/R 54.0 ± 4.0%; IPC 80.2 ± 6.3%). This protective effect was abolished by NOS inhibitor N G -nitro-L-arginine methyl ester and not changed by ascorbic acid. Electron microscopy showed marked endothelial damage after I/R and the ultrastructural changes were prevented by delayed preconditioning. Following I/R, the impairment of eNOS phosphorylation and expression was observed in mesenteric vessels. Furthermore, phosphatidylinositol 3-kinase (PI3K) and Akt phosphorylation were reduced, although total PI3K and Akt remained unchanged. IPC restored I/R-induced impairment of eNOS expression and activity. This was possibly the result of the recovery of PI3K/Akt phosphorylation. Furthermore, I/R increased serum level of malondialdehyde, intravascular superoxide and nitrotyrosine generation, which were abrogated by IPC. These results suggest that delayed preconditioning prevented I/R-induced endothelial injury in peripheral resistance vasculature, both in terms of functional and structural changes. Endothelial protection afforded by delayed IPC is associated with inhibition of oxidative stress and upregulation of PI3K/Akt/eNOS pathway.

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Section: Hematoxylin and Eosin Staining And Immunohistochemistrymentioning

confidence: 99%

Delayed preconditioning prevents ischemia/reperfusion-induced endothelial injury in rats: role of ROS and eNOS

Zhao

et al. 2013

Laboratory Investigation

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“…A left intercostal thoracotomy was performed to expose the heart, and the left anterior descending artery (LAD) was ligated at the origin as previously described (Wang et al 2010;Wen et al 2011). The sham group underwent thoracotomy and pericardiotomy, but not LAD ligation.…”

Section: Surgical Proceduresmentioning

confidence: 99%

Artemisinin Attenuates Post-Infarct Myocardial Remodeling by Down-Regulating the NF-κB Pathway

Wang

et al. 2012

Tohoku J. Exp. Med.

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Myocardial infarction (MI) leads to progressive left ventricular (LV) dilatation and is associated with interstitial fibrosis in the non-infarcted myocardium. The NF-κB signaling pathway plays an important role in ventricular remodeling after MI. Recent studies have indicated that the anti-malarial agent artemisinin can inhibit NF-κB activation, which may attenuate post-infarct myocardial remodeling. In this study, we investigated the effect of artemisinin on post-infarct myocardial remodeling using a rat model of MI. Adult male Sprague Dawley rats were divided into a sham group (n = 10) and MI groups that were treated either with oral gavage of artemisinin (75 mg/kg/day, n = 20) or vehicle (0.5% carboxymethyl cellulose, n = 20) three times a day for 4 weeks. Each treatment was started at 24 hours after ligation of the left anterior descending coronary artery. Four weeks after MI, the artemisinin-treated group showed a significantly improved survival rate compared with that of the vehicle-treated group (65% vs. 40%, P < 0.05). Although infarct size was similar in both groups, echocardiography showed significant improvements in cardiac function and left ventricular dimensions in the artemisinin-treated group. Moreover, the degree of myocardial fibrosis and elevated levels of fibrosis-related factors [transforming growth factor-β1, collagen type I, matrix metalloproteinase (MMP)-2 and MMP-9] in the non-infarcted myocardium were remarkably ameliorated by artemisinin (all P < 0.05). Importantly, artemisinin inhibited the NF-κB pathway by blocking IKBα phosphorylation. In conclusion, artemisinin may attenuate post-infarct myocardial remodeling by down-regulating the NF-κB pathway.

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“…The withdrawal of ET-mediated vasoconstriction during exercise in the normal heart was shown to be mediated by NO and prostanoids (37); these data indicate that recruitment of coronary flow reserve during exercise depends critically on a healthy well-functioning endothelium. Since endothelial dysfunction has been shown to be present after MI (4,47,49), we investigated in the present study if the contributions of the three main endothelial vasoactive systems (NO, prostanoids, and ET) to control of coronary resistance vessel tone in remodeled myocardium were altered at rest and/or during exercise.…”

Section: Integrated Endothelial Control Of Coronary Resistance Vesselmentioning

confidence: 99%

Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction

Beer

Taverne

Kuster

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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de Beer VJ, Taverne YJ, Kuster DW, Najafi A, Duncker DJ, Merkus D. Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction. Am J Physiol Heart Circ Physiol 301: H1080 -H1089, 2011. First published June 17, 2011 doi:10.1152/ajpheart.01307.2010 is associated with endothelial dysfunction resulting in an imbalance in endothelium-derived vasodilators and vasoconstrictors. We have previously shown that despite increased endothelin (ET) plasma levels, the coronary vasoconstrictor effect of endogenous ET is abolished after MI. In normal swine, nitric oxide (NO) and prostanoids modulate the vasoconstrictor effect of ET. In light of the interaction among NO, prostanoids, and ET combined with endothelial dysfunction present after MI, we investigated this interaction in control of coronary vasomotor tone in the remote noninfarcted myocardium after MI. Studies were performed in chronically instrumented swine (18 normal swine; 13 swine with MI) at rest and during treadmill exercise. Furthermore, endothelial nitric oxide synthase (eNOS) and cyclooxygenase protein levels were measured in the anterior (noninfarcted) wall of six normal and six swine with MI. eNOS inhibition with N -nitro-L-arginine (L-NNA) and cyclooxygenase inhibition with indomethacin each resulted in coronary vasoconstriction at rest and during exercise, as evidenced by a decrease in coronary venous oxygen levels. The effect of L-NNA was slightly decreased in swine with MI, although eNOS expression was not altered. Conversely, in accordance with the unaltered expression of cyclooxygenase-1 after MI, the effect of indomethacin was similar in normal and MI swine. L-NNA enhanced the vasodilator effect of the ETA/B receptor blocker tezosentan but exclusively during exercise in both normal and MI swine. Interestingly, this effect of L-NNA was blunted in MI compared with normal swine. In contrast, whereas indomethacin increased the vasodilator effect of tezosentan only during exercise in normal swine, indomethacin unmasked a coronary vasodilator effect of tezosentan in MI swine both at rest and during exercise. In conclusion, the present study shows that endothelial control of the coronary vasculature is altered in post-MI remodeled myocardium. Thus the overall vasodilator influences of NO as well as its inhibition of the vasoconstrictor influence of ET on the coronary resistance vessels were reduced after MI. In contrast, while the overall prostanoid vasodilator influence was maintained, its inhibition of ET vasoconstrictor influences was enhanced in post-MI remote myocardium. endothelin; nitric oxide; prostacyclin CONGESTIVE HEART FAILURE IS the only major cardiovascular disorder of which the incidence has increased over the past decade, which is principally due to a reduction in mortality associated with acute myocardial infarction (MI). Consequently, MI has become an increasingly important risk factor for the development of congestive heart failure (5). The loss of viable myocardial tissue and the consequent left ve...

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Exercise improves the dilatation function of mesenteric arteries in postmyocardial infarction rats via a PI3K/Akt/eNOS pathway-mediated mechanism

Cited by 48 publications

References 56 publications

Delayed preconditioning prevents ischemia/reperfusion-induced endothelial injury in rats: role of ROS and eNOS

Delayed preconditioning prevents ischemia/reperfusion-induced endothelial injury in rats: role of ROS and eNOS

Artemisinin Attenuates Post-Infarct Myocardial Remodeling by Down-Regulating the NF-κB Pathway

Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction

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