Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0729233 (Thoracic)
 6,478 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to determine whether increased expression of heme oxygenase (HO) contributes to impairment of aortic contractile responses after hypoxia through effects on reactivity to endothelin-1 (ET-1). Thoracic aortas from normoxic rats and rats exposed to hypoxia (10% O2) for 16 or 48 h were mounted in organ bath myographs for contractile studies, fixed in paraformaldehyde, or frozen in liquid nitrogen for protein extraction. In rings from normoxic rats, the HO inhibitor tin protoporphyrin IX (SnPP IX, 10 microM) did not alter the response to phenylephrine or ET-1. In rings from rats exposed to 16-h hypoxia, maximum tension generated in response to these agonists was higher in endothelium-intact but not -denuded rings in the presence of SnPP IX. In rings from rats exposed to 48-h hypoxia SnPP IX increased contraction in endothelium-intact but not -denuded rings. In endothelium-intact aortic rings from rats exposed to 16-h hypoxia incubated with endothelin A receptor-specific antagonist BQ-123 (10(-7) M), SnPP IX did not alter phenylephrine-induced contraction. Aortic ET-1 protein levels, measured by radioimmunoassay, were increased in rats exposed to hypoxia for 16 and 48 h. Western blotting showed that HO-1 and HO-2 protein were increased after 16 h of hypoxia and returned to near-control levels after 48 h. Increase in HO-1 protein was detected in endothelium-intact and -denuded rings. Removal of endothelium abolished the increase in HO-2 immunoreactivity. Immunohistochemistry localized expression of HO-1 protein to vascular smooth muscle, whereas HO-2 was only detected in endothelium. HO-2 is expressed by aortic endothelial cells early during hypoxic exposure and impairs ET-1-mediated potentiation of contraction to alpha-adrenoceptor stimulation.
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PMID:Interaction between endothelial heme oxygenase-2 and endothelin-1 in altered aortic reactivity after hypoxia in rats. 1548 27

1. The aims of the present study were to explore the protective effect of curcumin against the acute vascular endothelial dysfunction induced by high glucose and to investigate the possible role of heme oxygenase (HO)-1 in this protective action. 2. Thoracic aortic rings, with or without endothelium, obtained from male Sprague-Dawley rats were mounted in an organ bath. Isometric contraction of the rings was recorded. After completion of the organ bath studies, rings were homogenized and centrifuged (30,000 g, 4 degrees C, 15 min) and HO activity was determined in the supernatant. 3. After 2 h incubation of aortic rings in the presence of high glucose (44 mmol/L), the relaxation evoked by acetylcholine (3 x 10(-8) to 3 x 10(-5) mol/L) was significantly decreased only in rings with an intact endothelium. When rings were coincubated in the presence of curcumin (10(-13) to 10(-11) mol/L) and high glucose, curcumin reversed the vasodilator dysfunction induced by high glucose dose dependently. 4. Curcumin (10(-11) mol/L) increased HO activity in the aortic rings compared with activity in control rings (63.1 +/- 3.6 vs control 43.2 +/- 2.9 pmol/mg per h, respectively; P < 0.01). Protoporphyrin IX zinc (10(-6) mol/L), an inhibitor of HO-1, offset the protective effects of curcumin. In addition, the non-selective guanylate cyclase (GC) inhibitor methylene blue (10(-6) mol/L) completely abolished the protective effects of curcumin. 5. In conclusion, the results of the present study show that curcumin alleviates the acute endothelium-dependent vasodilator dysfunction induced by high glucose in rat aortic rings. Increased HO-1 activity and stimulation of GC may be involved in the protective effects of curcumin.
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PMID:Curcumin ameliorates high glucose-induced acute vascular endothelial dysfunction in rat thoracic aorta. 1947 93