Chronic protection against ischemia and reperfusion-induced endothelial dysfunction during therapy with different organic nitrates

2012 ◽  
Vol 101 (6) ◽  
pp. 453-459 ◽  
Author(s):  
Monica Lisi ◽  
Matthias Oelze ◽  
Saverio Dragoni ◽  
Andrew Liuni ◽  
Sebastian Steven ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Organic Nitrates ◽  
Ischemia And Reperfusion

Endothelial Dysfunction After Brain Ischemia and Reperfusion

2001 ◽  
pp. 64-69
Author(s):  
Timur D. Vlasov ◽  
Victor I. Amosov ◽  
Dmitry E. Korzhevski
Keyword(s):  
Endothelial Dysfunction ◽  
Brain Ischemia ◽  
Ischemia And Reperfusion

scholarly journals Endothelial dysfunction: Mechanisms of development and therapeutic options

2006 ◽  
Vol 59 (7-8) ◽  
pp. 335-341 ◽  
Author(s):  
Srdjan Pesic ◽  
Miroslav Radenkovic ◽  
Leposava Grbovic
Keyword(s):  
Endothelial Dysfunction ◽  
Ace Inhibitors ◽  
Vascular Endothelial Cells ◽  
Beta Blockers ◽  
Phosphodiesterase Inhibitors ◽  
Initial Step ◽  
Endothelial Damage ◽  
Lipid Lowering ◽  
Organic Nitrates ◽  
Vascular Protection

Introduction. Vascular endothelial cells play a key role in cardiovascular regulation by producing a number of potent vasoactive agents, including the vasodilator molecule nitric oxide (NO) and the vasoconstrictor peptide endothelin (ET). Endothelial dysfunction. Endothelial dysfunction is recognized as the initial step in the atherosclerotic process. Impairment of NO synthesis, or increased inactivation of NO by superoxide radicals, may account for the increased peripheral vascular tone, as well as contribute to the clinical consequences of different pathophysiological conditions-which include vascular hypertrophy, increased platelet and monocyte adhesion to the endothelium, atherosclerosis, myocardial infarction and stroke. To date, most interventions attempting to improve endothelial dysfunction have targeted one or more of the numerous risk factors that can cause endothelial damage: hypertension (ACE inhibitors and calcium antagonists), hypercholesterolemia (lipid-lowering agents), cigarette smoking (cessation), sedentary lifestyle (increased physical activity), menopause (estrogen replacement therapy), and diabetes mellitus (control of metabolic abnormalities). Several pharmacologic agents have been suggested to achieve vascular protection through mechanisms that go beyond their primary therapeutic actions (ACE-and HMG-CoA reductase inhibitors). Beneficial changes to the endothelium might result from promotion of vasorelaxation, inhibition of vasoconstriction, reduction in the production of free radicals, or other mechanisms that protect the endothelium from injury. Conclusion. This study deals with the results of many experimental and clinical investigations. The possibility of using different classes of drugs was also established, including ACE inhibitors, Ca-antagonists, AT and endothelin receptor antagonists, direct activator of adenyl cyclase, statins, antioxidants, L-arginine, phosphodiesterase inhibitors, beta-blockers and organic nitrates. .

scholarly journals Sildenafil Prevents Endothelial Dysfunction Induced by Ischemia and Reperfusion via Opening of Adenosine Triphosphate–Sensitive Potassium Channels

Circulation ◽  
2005 ◽  
Vol 111 (6) ◽  
pp. 742-746 ◽  
Author(s):  
Tommaso Gori ◽  
Silvia Sicuro ◽  
Saverio Dragoni ◽  
Giovanni Donati ◽  
Sandro Forconi ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Potassium Channels ◽  
Adenosine Triphosphate ◽  
Ischemia And Reperfusion

Folic Acid Does Not Limit Endothelial Dysfunction Induced by Ischemia and Reperfusion

2005 ◽  
Vol 46 (4) ◽  
pp. 494-497 ◽  
Author(s):  
Saverio Dragoni ◽  
Tommaso Gori ◽  
Giuseppe Di Stolfo ◽  
Silvia Sicuro ◽  
Sandro Forconi ◽  
...  
Keyword(s):  
Folic Acid ◽  
Endothelial Dysfunction ◽  
Ischemia And Reperfusion

scholarly journals Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Andreas Daiber ◽  
Matthias Oelze ◽  
Philip Wenzel ◽  
Franziska Bollmann ◽  
Andrea Pautz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Side Effects ◽  
Endothelial Dysfunction ◽  
Heme Oxygenase ◽  
Nitrate Tolerance ◽  
Heme Oxygenase 1 ◽  
Organic Nitrate ◽  
Organic Nitrates ◽  
Beneficial Effects ◽  
Vascular Oxidative Stress

Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction, and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents, and this phenomenon is largely based on induction of oxidative stress with subsequent endothelial dysfunction. We therefore speculated that induction of heme oxygenase-1 (HO-1) could be an efficient strategy to overcome nitrate tolerance and the associated side effects. Indeed, we found that hemin cotreatment prevented the development of nitrate tolerance and vascular oxidative stress in response to chronic nitroglycerin therapy. Vice versa, pentaerithrityl tetranitrate (PETN), a nitrate that was previously reported to be devoid of adverse side effects, displayed tolerance and oxidative stress when the HO-1 pathway was blocked pharmacologically or genetically by using HO-1+/–mice. Recently, we identified activation of Nrf2 and HuR as a principle mechanism of HO-1 induction by PETN. With the present paper, we present and discuss our recent and previous findings on the role of HO-1 for the prevention of nitroglycerin-induced nitrate tolerance and for the beneficial effects of PETN therapy.

Postconditioning fails to prevent radial artery endothelial dysfunction induced by ischemia and reperfusion: evidence from a human in vivo study

2006 ◽  
Vol 84 (6) ◽  
pp. 611-615 ◽  
Author(s):  
Saverio Dragoni ◽  
Giuseppe Di Stolfo ◽  
Silvia Sicuro ◽  
Monica Lisi ◽  
John D. Parker ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Radial Artery ◽  
Tissue Damage ◽  
Animal Studies ◽  
In Vivo Model ◽  
Ischemia And Reperfusion ◽  
Ischemic Tissue ◽  
Before And After ◽  
Dependent Flow

Animal studies have shown that, as compared with unrestricted reperfusion, exposure to brief periods of controlled ischemia (postconditioning) at the end of a prolonged ischemia reduces the extent of tissue damage. We set out to test whether postconditioning can prevent endothelial dysfunction induced by ischemia and reperfusion in a human in vivo model. Ten healthy young non-smoking volunteers were enrolled in this cross-over, controlled, investigator-blinded study. Subjects were exposed to 15 min of forearm ischemia followed by either unrestricted reperfusion or postconditioning (3 periods of 20 s of ischemia separated by 10 s of reperfusion). Endothelium-dependent flow-mediated dilation (FMD) was measured at the level of the radial artery before and after ischemia (with or without postconditioning). Forearm ischemia blunted FMD in both study visits (unrestricted reperfusion visit: before ischemia, 7.7% ± 1.3%; after ischemia, 2.5% ± 1.4%; and postconditioning visit: before, 7.3% ± 1.2%; after, 2.6 ± 1.6%; P < 0.05 for both, P = not significant (NS) between visits). In contrast with data from animal studies, postconditioning (20 s ischemia – 10 s reperfusion repeated 3 times) does not limit post-ischemic endothelial dysfunction in this human in vivo model. Further human studies are necessary to evaluate other reperfusion protocols in an attempt to limit post-ischemic tissue damage.

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