| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
In endotoxemic animal models, the distribution of cardiac output is disturbed, with relative hyperperfusion in some regions and hypoperfusion in others. Altered release of endothelium-derived relaxing factors (EDRF/NO) has been proposed as a final common pathway underlying the abnormal vasodilator responses to lipopolysaccharide (LPS). Nitric oxide plays a major role in endothelium-dependent relaxations. In addition, endothelium-derived hyperpolarizing factor (EDHF), an unidentified diffusible substance distinct from nitric oxide contributes to endothelium-dependent relaxations by opening K+ channels in the underlying vascular smooth muscle. The present study was designed to elucidate the in vitro role of EDRFs (NO and EDHF) in vasodilation during septic shock. Male Sprague-Dawley rats were treated with either an intraperitoneal injection of LPS (50 mg kg^<-1>), and septicemia in LPS-treated rats was confirmed by measuring serum concentration of endotoxin. The isometric tension, the membrane potential of smooth muscle cells, and tissue levels of cyclic GMP (using enzyme immunoassay) and iNOS protein (using Western blot analysis) were measured in the arterial tree of the animals. In the LPS-treated rat, the level of cyclic GMP was significantly grater in mesenteric artery than those in aorta, carotid and renal arteries. In the presence of L-arginine, the cyclic GMP concentration in the aorta and mesenteric arteries, but not the carotid or renal arteries, was increased. Expression of iNOS protein was induced in the blood vessels of LPS-treated rats. However, the expression levels of iNOS protein were not singificantly different among those blood vessels. These results indicate that a heterogeneity of cyclic GMP levels among arterial trees and a discrepancy between tissue cyclic GMP and iNOS protein levels of the rat blood vessels with endotoxemia.
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