Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The binding characteristics and localization of bosentan, an orally active endothelin-1 (ET-1) antagonist, were studied on sections of human coronary artery by in vitro autoradiography. Competition studies were performed to determine the ability of bosentan to prevent [125I]ET-1 binding to the coronary vasculature. The effects of bosentan on ET-1-induced contraction of the coronary artery were also studied in vitro. [3H]Bosentan bound to the tunica media of the human coronary artery. Unlabeled bosentan prevented [125I]ET-1 binding to this vessel in a concentration-dependent manner, and functional studies indicated that bosentan antagonizes ET-1--induced constriction. These data show that bosentan is able to reduce ET-1 binding to the human coronary artery and ET-1 constrictor effects in vitro. Bosentan is an orally active ET-1 antagonist, and these results suggest that this compound might be used to block the effects of locally released ET-1 in pathologic conditions, such as atherosclerosis, angina, and myocardial ischemia.
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PMID:[3H]bosentan binding to human coronary artery: functional correlates. 858 20

Bosentan is the first endothelin (ET) receptor antagonist approved by the Food and Drug Administration for the management of pulmonary arterial hypertension (PAH). In patients with World Health Organization Class III and IV PAH, bosentan has demonstrated improvement in dyspnea and exercise tolerance. ET also plays an important role in the pathophysiology of different vascular diseases. Therefore, bosentan also may have the potential to alter the outcome of many other diseases, such as heart failure, hypertension, ischemic heart disease, and renal disease, as well as cerebrovascular disorders. Because of the rarity and the poor prognosis of patients with PAH, as well as the requirement of close monitoring of bosentan (due to its potential of causing liver dysfunction and its teratogenic effects), bosentan is currently available only through a special access program and is distributed by certain selected pharmacies. Patients who are receiving bosentan should be taught to recognize early signs and symptoms of liver dysfunction and possible pregnancy. In addition, bosentan is not only a substrate but also an inducer of CYP3A4 and CYP2C9. Therefore, it is anticipated that numerous drug interactions may occur. Patients should be advised to consult their physicians or pharmacists should they need to consume other prescription or nonprescription medications.
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PMID:Bosentan. 1271 83

Endothelin-1 has been shown to be associated with greater myocardial ischemia and reperfusion injury in which oxidative stress plays a key role. The efficacy of bosentan, a mixed ETA-ETB endothelin receptor antagonist, in protecting the myocardium from ischemia-reperfusion injury and oxidative stress was studied in open-chest Wistar rats. Anesthetized adult male rats (175-250 g b wt) underwent sham operation (SHAM group) or were subjected to 40 min of myocardial ischemia (MI) induced by temporary occlusion of the left anterior descending coronary artery (LAD) followed by 2 h reperfusion (R). Rats submitted to the MI-R protocol were administered bosentan at a dose of 3 mg/kg i.v. 20 min (BOS group) or saline (CON group) 20 min post-occlusion of LAD. After the 2 h reperfusion period the animals were euthanized and the heart rapidly excised. Cardiac tissue samples were snap frozen in liquid nitrogen for biochemical assay and were fixed in 10% formalin solution for histologic evaluation. Myocardial I-R resulted in a significant increase (p < 0.05) in the myocardial malondialdehyde levels and a decrease (p < 0.01) in the myocardial reduced glutathione content. These changes were associated with significant decreases in the myocardial activity of antioxidant enzymes superoxide dismutase (p < 0.05) and catalase (p < 0.01) and severe tissue damage in the jeopardized myocardium in the CON group as compared with the non-myocardial ischemia-reperfusion (NMI-R) SHAM group. Bosentan exerted marked tissue protective effect as assessed by histologic evaluation of the myocardium. The drug significantly (p < 0.05) attenuated myocardial oxidative stress and restored the cellular antioxidant defense mechanisms as compared with the saline-treated controls subjected to the MI-R protocol. Furthermore, bosentan also exerted a marked effect on peripheral hemodynamics and heart rate during the reperfusion phase (data reported elsewhere). These results are consistent with the concept that endothelin-1 may be involved in the pathogenesis of myocardial ischemia and infarction. This study demonstrates the antioxidant effect of non-selective endothelin receptor antagonism elucidating that, part of the aetiology of ischemia and reperfusion induced myocardial injury involves impaired antioxidant defenses.
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PMID:Bosentan, the mixed ETA-ETB endothelin receptor antagonist, attenuated oxidative stress after experimental myocardial ischemia and reperfusion. 1633 85