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)

Ten-day administration of the glutamate-cysteine ligase inhibitor L-buthionine-[S,R]-sulfoximine (BSO; 20 or 30 mM in drinking water) to adult male Sprague-Dawley rats induced 50-60% glutathione depletion (p<0.001) and elevated aortic ring reactive oxygen species release and tissue and plasma H2O2 concentrations (p<0.001) compared to control animals (CON) that consumed normal drinking water. In contrast to previous studies using tail cuff plethysmography methods, BSO had no significant effect on systolic blood pressure assessed by indwelling femoral artery catheters in conscious animals (10-day values, 119+/-3 mn Hg vs 122+/-4 mm Hg in CON vs BSO, respectively). Thoracic aorta rings were excised for in vitro assessment of vasomotor function. BSO shifted the phenylephrine (PE) dose-response curve to the left (p=0.003), lowering the EC50 for PE contraction (from -6.752+/-0.056 to -7.056+/-0.055 log units; p=0.001). Endothelium-dependent relaxation to acetylcholine (ACh) was significantly blunted (p=0.019) and the EC50 for ACh relaxation was significantly increased (from -7.428+/-0.117 to -7.129+/-0.048 log units; p=0.02) in BSO vs CON. Endothelium-independent vasorelaxation to sodium nitroprusside was similar in BSO and CON groups. Thoracic aorta immunoblot analyses revealed increases in endothelial nitric oxide synthase, superoxide dismutase 1 and 2, and soluble guanylate cyclase in BSO vs CON (all p<0.01). Thus, enhanced PE contraction, blunted endothelium-dependent relaxation, and adaptations in nitric oxide bioavailability pathways provide the first evidence of chronic, in vivo BSO-induced, oxidative stress-mediated direct effects on the vasomotor function of arteries.
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PMID:Glutathione depletion in vivo enhances contraction and attenuates endothelium-dependent relaxation of isolated rat aorta. 1645 98

High salt intake produces vascular changes that contribute to the development of hypertension in salt-sensitive individuals. Because reactive oxygen species play a role in the pathogenesis of cardiovascular diseases, we investigated whether oxidative stress contributes to salt-sensitive hypertension. Sprague-Dawley rats were divided in different groups and received tap water (vehicle), 30 mmol/L of l-buthionine sulfoximine ([BSO] an oxidant), high salt ([HS] 1% NaCl), and BSO plus HS without and with antioxidant tempol (1 mmol/L) in drinking water for 12 days. Compared with vehicle, BSO treatment caused oxidative stress and mild increase in blood pressure. Thoracic aortic rings from BSO-treated rats exhibited decreased response to endothelium-independent vasorelaxants. In HS-treated rats, the response to vasoactive agents, as well as blood pressure, was unaffected. Concomitant treatment of rats with BSO and HS produced a marked increase in blood pressure and a decreased response to both endothelium-dependent and endothelium-independent vasorelaxants with an increase in EC(50). Incubation of aortic tissue from BSO-treated rats with sodium nitroprusside showed decreased cGMP accumulation, whereas HS rats had decreased basal NO synthase activity. Tempol decreased oxidative stress, normalized blood pressure, and restored NO signaling and responses to vasoactive compounds in BSO and BSO plus HS rats. We conclude that BSO increases oxidative stress and reduces NO signaling, whereas HS reduces NO levels by decreasing the NO synthase activity. These phenomena collectively result in reduced responsiveness to both endothelium -dependent and endothelium- independent vasorelaxants and may contribute to salt-sensitive hypertension.
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PMID:Mechanisms of oxidative stress-induced increase in salt sensitivity and development of hypertension in Sprague-Dawley rats. 1720 Apr 36