Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Dec 2006
Altered L-arginine/nitric oxide synthase/nitric oxide pathway in the vascular adventitia of rats with sepsis.
1. In recent studies, the vascular adventitia has been established as an important source of inducible nitric oxide synthase (iNOS) and subsequent nitric oxide (NO) production, even more powerful than the media in response to certain inflammatory factors, such as lipopolysaccharide (LPS). The adventitia has an independent L-arginine (L-Arg)/NOS/NO pathway and is involved in the regulation of vascular function. ⋯ The NO levels in the plasma and incubation media (incubation for 40 min) in the sepsis group were increased by 144 and 273%, respectively (both P < 0.01). 6. The Arg/NOS/NO pathway was activated in the vascular adventitia of rats with sepsis shock. The L-Arg/NOS/NO pathway in the aortic adventitia may play an important role in the pathogenesis of sepsis and septic shock.
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Clin. Exp. Pharmacol. Physiol. · Nov 2006
Edaravone reduces myocardial infarct size and improves cardiac function and remodelling in rabbits.
1. In the present study, we investigated the effect of 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone), a free radical scavenger, on myocardial infarct (MI) size and cardiac function in an in vivo model of MI in rabbits. We further investigated the contribution of hydroxyl radicals, superoxide and nitric oxide (NO) to its effects. 2. ⋯ Dihydroethidium staining showing in situ detection of superoxide was less intense in ischaemic myocardium in the edaravone-treated group compared with the control group. Edaravone improved cardiac function and left ventricular remodelling 14 days after infarction. 5. In conclusion, edaravone significantly reduces MI size and improves cardiac function and LV remodelling by decreasing hydroxyl radicals and superoxide in the myocardium and increasing the production of NO during reperfusion in rabbits.
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Clin. Exp. Pharmacol. Physiol. · Nov 2006
Effects of trolox on nerve dysfunction, thermal hyperalgesia and oxidative stress in experimental diabetic neuropathy.
1. Diabetic neuropathy is one of the most common complications of diabetes and oxidative stress has been implicated to play a major role in its pathophysiology. 2. In the present study, we targeted oxidative stress using trolox, an anti-oxidant, in streptozotocin-induced diabetic neuropathy in rats. 3. ⋯ Two weeks treatment with trolox (10 and 30 mg/kg, i.p.) started on completion of the 6th week of diabetes significantly improved MNCV, NBF and inhibited thermal hyperalgesia. Trolox treatment also improved the activity of anti-oxidant enzymes and inhibited lipid peroxidation in sciatic nerves of diabetic rats. 6. The results of the present study suggest the beneficial effects of trolox in experimental diabetic neuropathy.
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Clin. Exp. Pharmacol. Physiol. · Oct 2006
ReviewRenal oxygen delivery: matching delivery to metabolic demand.
The kidneys are second only to the heart in terms of O2 consumption; however, relative to other organs, the kidneys receive a very high blood flow and oxygen extraction in the healthy kidney is low. Despite low arterial-venous O2 extraction, the kidneys are particularly susceptible to hypoxic injury and much interest surrounds the role of renal hypoxia in the development and progression of both acute and chronic renal disease. ⋯ A number of such mechanisms specific to the kidney are reviewed herein, including the relationship between renal blood flow and O2 consumption, pre- and post-glomerular arterial-venous O2 shunting, tubulovascular cross-talk, the differential control of regional kidney blood flow and the tubuloglomerular feedback mechanism. The roles of these mechanisms in the control of renal oxygenation, as well as how dysfunction of these mechanisms may lead to renal hypoxia, are discussed.
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Clin. Exp. Pharmacol. Physiol. · Oct 2006
ReviewHypoxia-induced erythropoietin production: a paradigm for oxygen-regulated gene expression.
The mechanisms controlling the expression of the gene encoding for the hormone erythropoietin (EPO) are exemplary for oxygen-regulated gene expression. In humans and other mammals, hypoxia modulates EPO levels by increasing expression of the EPO gene. An association between polycythaemia and people living at high altitudes was first reported more than 100 years ago. ⋯ In addition to erythropoiesis, HIF-1 regulates a broad range of physiologically relevant genes involved in angiogenesis, apoptosis, vasomotor control and energy metabolism. Therefore, the HIF system is implicated in the pathophysiology of many human diseases. In addition to the tight regulation by oxygen tension, temporal and tissue-specific signals limit expression of the EPO gene primarily to the fetal liver and the adult kidney.