American journal of physiology. Heart and circulatory physiology
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Am. J. Physiol. Heart Circ. Physiol. · Mar 2001
Overexpression of cardiac I-kappaBalpha prevents endotoxin-induced myocardial dysfunction.
Nuclear factor-kappa B (NF-kappaB) is an inducible transcription factor that regulates expression of many genes, such as tumor necrosis factor-alpha (TNF-alpha), which may contribute to myocardial dysfunction. We investigated whether cardiac NF-kappaB activation is involved in the development of myocardial dysfunction after lipopolysaccharide (LPS) challenge. Mice were intraperitoneally injected with LPS, and the hearts were harvested and assayed for NF-kappaB translocation. ⋯ When whole hearts were excised, perfused in a Langendorff preparation, and challenged with endotoxin, I-kappaBalphaDeltaN transgenic hearts displayed normal cardiac function, whereas profound contractile dysfunction was observed in wild-type hearts. These data indicate that myocardial NF-kappaB translocates within minutes after LPS administration. Inhibition of myocyte NF-kappaB activation by overexpression of myocyte I-kappaBalpha is sufficient to block cardiac TNF-alpha production and prevent cardiac dysfunction after LPS challenge.
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Am. J. Physiol. Heart Circ. Physiol. · Mar 2001
Endothelium-independent, ouabain-sensitive relaxation of bovine coronary arteries by EETs.
Endothelium-derived hyperpolarizing factor (EDHF) is released in response to agonists such as ACh and bradykinin and regulates vascular smooth muscle tone. Several studies have indicated that ouabain blocks agonist-induced, endothelium-dependent hyperpolarization of smooth muscle. We have demonstrated that epoxyeicosatrienoic acids (EETs), cytochrome P-450 metabolites of arachidonic acid, function as EDHFs. ⋯ Ouabain did not change NP(o) but blocked the 14,15-EET-induced increase in NP(o). These results indicate that: 1) EETs relax coronary arteries in an endothelium-independent manner, 2) unlike EETs, potassium chloride does not relax the coronary artery, and 3) ouabain inhibits bradykinin- and EET-induced relaxations as has been reported for EDHF. These findings provide further evidence that EETs are EDHFs.