Influence of secretin and l-NAME on vascular permeability in the coronary circulation of intact and diabetic rats

Sitniewska, Ewa; Rj, Wiśniewska

doi:10.1016/s0167-0115(00)00131-2

Cited by 8 publications

(6 citation statements)

References 39 publications

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“…No significant FITC signals were noted in intact hearts from animals injected with FITC or FITC-NP without IR procedure (data not shown). In IR hearts from animals injected intravenously with FITC-NP and with Evans blue, we examined the localization of FITC and Evans blue and found that the distribution of Evans blue was closely correlated with the distribution of FITC ( Fig 2D ), suggesting a role of enhanced vascular permeability in the mechanism of PLGA nanoparticle delivery to the IR cardiomyocytes [ 23 ]. Flow cytometry of the IR heart and blood 24-hour after IR and FITC-NP treatment revealed that CD11b-positive leukocytes in the IR heart and blood had significant FITC signals ( Fig 2E ), suggesting that PLGA nanoparticle were delivered to CD11b-positive leukocytes in the circulation and in the IR myocardium.…”

Section: Resultsmentioning

confidence: 99%

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A New Therapeutic Modality for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin Induces Cardioprotection from Ischemia-Reperfusion Injury via Activation of PI3K/Akt Pathway and Anti-Inflammation in a Rat Model

et al. 2015

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AimThere is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction (AMI), for which the effectiveness of interventional reperfusion therapy is hampered by myocardial ischemia-reperfusion (IR) injury. Pretreatment with statins before ischemia is shown to reduce MI size in animals. However, no benefit was found in animals and patients with AMI when administered at the time of reperfusion, suggesting insufficient drug targeting into the IR myocardium. Here we tested the hypothesis that nanoparticle-mediated targeting of pitavastatin protects the heart from IR injury.Methods and ResultsIn a rat IR model, poly(lactic acid/glycolic acid) (PLGA) nanoparticle incorporating FITC accumulated in the IR myocardium through enhanced vascular permeability, and in CD11b-positive leukocytes in the IR myocardium and peripheral blood after intravenous treatment. Intravenous treatment with PLGA nanoparticle containing pitavastatin (Pitavastatin-NP, 1 mg/kg) at reperfusion reduced MI size after 24 hours and ameliorated left ventricular dysfunction 4-week after reperfusion; by contrast, pitavastatin alone (as high as 10 mg/kg) showed no therapeutic effects. The therapeutic effects of Pitavastatin-NP were blunted by a PI3K inhibitor wortmannin, but not by a mitochondrial permeability transition pore inhibitor cyclosporine A. Pitavastatin-NP induced phosphorylation of Akt and GSK3β, and inhibited inflammation and cardiomyocyte apoptosis in the IR myocardium.ConclusionsNanoparticle-mediated targeting of pitavastatin induced cardioprotection from IR injury by activation of PI3K/Akt pathway and inhibition of inflammation and cardiomyocyte death in this model. This strategy can be developed as an innovative cardioprotective modality that may advance currently unsatisfactory reperfusion therapy for AMI.

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Section: Resultsmentioning

confidence: 99%

“…Vascular permeability was measured by dye extraction method as previously described [ 23 , 24 ]. In brief, Evans blue dye diluted in saline at 30 mg/mL was injected via femoral vein 2.5 hours after reperfusion.…”

Section: Methodsmentioning

confidence: 99%

A New Therapeutic Modality for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin Induces Cardioprotection from Ischemia-Reperfusion Injury via Activation of PI3K/Akt Pathway and Anti-Inflammation in a Rat Model

et al. 2015

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“…The changes in permeability of cardiac tissue are best accomplished with histologic techniques or with studies of isolated perfused coronary venules. Such approaches have been previously used to demonstrate diabetes-related increase in permeability of coronary microvasclature to albumin (21)(22)(23) The precise mechanisms responsible for these observations are not clear. One potential explanation is that statins alter rho-GTPase activity (11,24 -28), and rho signaling pathways have been shown to have a critical role in endothelial barrier function (9,10).…”

Section: Discussionmentioning

confidence: 99%

Statins Ameliorate Endothelial Barrier Permeability Changes in the Cerebral Tissue of Streptozotocin-Induced Diabetic Rats

et al. 2005

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Statins may have favorable effects on endothelial barrier function. The effect of rosuvastatin and simvastatin therapy (10 mg/kg) for 5 weeks on blood-brain barrier (BBB), blood-retinal barrier (BRB), and cardiac muscle permeability of streptozotocin-induced diabetic rats was studied. The size-selective permeability of different vascular beds to a group of fluorescein isothiocyanate dextrans of varying molecular weights was measured. The volume of distribution of 250-, 70-, and 40-kDa dextrans in the cerebral tissue of diabetic rats were significantly increased. The volume of distribution of these dextrans in cerebral tissue was normalized by both statins. Diabetes did not significantly alter the BRB, but both statins decreased the volume of distribution of 70-and 40-kDa dextrans in the retina. The volume of distribution of 40 kDa in cardiac muscle was increased in diabetes, and this change was prevented with statin treatment. Treatment with rosuvastatin and mevalonate (150 mg/kg in drinking water for 5 weeks) did not alter the volume of distribution measurements. We concluded that 1) diabetes in rats is associated with significant changes in the BBB permeability; 2) statin treatment improves the endothelial barrier function in cerebral tissue, retina, and cardiac muscle; and 3) this statin effect could not be attributed to HMGCoA reductase inhibition. Diabetes 54: [2977][2978][2979][2980][2981][2982] 2005 O ne of the sentinel features of atherosclerosis is endothelial cell dysfunction that manifests itself in a variety of ways including poor nitric oxide production, poor vasodilatory response, and increased adhesiveness to leukocytes (1). Another potential endothelial dysfunction commonly observed in diabetes is altered permeability to macromolecules.Diabetes in humans and in animal models has been found to cause significant alterations in endothelial permeability in various vascular beds (2-5). Potential mechanisms underlying the diabetes-related changes in the blood-brain barrier (BBB) include altered expression of key structural and enzymatic proteins, alterations in the lipid composition and fluidity of the membranes, alterations in the neurotransmitter activity, and increased oxidative damage of the endothelial cells (2,6). Another likely contributor to these changes is the activation of protein kinase C that is shown to play an important role in increased permeability of the peripheral and cerebral circulation (7,8). Finally, recent studies have shown that inactivation of the rho-GTPase has a critical role in endothelial barrier function (9,10).Statins are known to have many pleiotropic effects (11). However, the effect of statins on the functional integrity of the microvasculature of diabetic animals has not been well studied. Statins are known to alter endothelial cell function, smooth muscle cell migration and proliferation, and some aspects of vascular inflammation (11). In addition, statins have been shown to improve endothelial barrier permeability in the aorta of Watanabe hyperlipidimic rabbits ...

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“…Because Evans blue binds to plasma albumin, this technique provides a reliable method of determining vascular permeability following I/R injury. This protocol has been used successfully by others and is reported to have a 24-h survival rate of 57% [25][26][27][28]. The inhibitors Go6976 and ML-7 were administered via the jugular vein to a circulatory concentration of 10 nM and 1 M respectively (based on calculated blood volume) 10 min prior to clamping of the left coronary artery.…”

Section: Induction Of I/r Injurymentioning

confidence: 99%

PKC and MLCK-Dependent, Cytokine-Induced Rat Coronary Endothelial Dysfunction

Tinsley

Hunter

Childs

2009

Journal of Surgical Research

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Influence of secretin and l-NAME on vascular permeability in the coronary circulation of intact and diabetic rats

Cited by 8 publications

References 39 publications

A New Therapeutic Modality for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin Induces Cardioprotection from Ischemia-Reperfusion Injury via Activation of PI3K/Akt Pathway and Anti-Inflammation in a Rat Model

A New Therapeutic Modality for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin Induces Cardioprotection from Ischemia-Reperfusion Injury via Activation of PI3K/Akt Pathway and Anti-Inflammation in a Rat Model

Statins Ameliorate Endothelial Barrier Permeability Changes in the Cerebral Tissue of Streptozotocin-Induced Diabetic Rats

PKC and MLCK-Dependent, Cytokine-Induced Rat Coronary Endothelial Dysfunction

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