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International Journal of Clinical Pharmacy - Background Diabetes mellitus is a complex multi-system disorder, requiring multi-disciplinary care. The conventional care model, where physicians are...  相似文献   
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BACKGROUND: Endothelium-dependent vascular relaxation is impaired in various disease states including hypertension. METHODS: We investigated whether a single bolus dose of clofibrate could rapidly reverse saline-induced endothelial dysfunction, in vivo, in salt-loaded Sprague-Dawley (S-D) rats. S-D rats, 5 weeks of age, were divided into two groups. One group served as a control (Con) and was given tap water; the other group (Sal) was given normal saline (0.9% NaCl) ad libitum for 3 weeks. RESULTS: Mean arterial pressure (MAP) was significantly higher (138 +/- 2 nu 112 +/- 2 mm Hg, P < .001), whereas the total plasma nitrite/nitrate levels were lower (1.7 +/- 0.3 v 2.8 +/- 0.2 micromol/L, P < .05) in Sal. At this time, endothelial function was assessed in vivo. Sal rats had decreased hypotensive responses to acetylcholine (ACh) but maintained normal responses to sodium nitroprusside. The ACh-induced hypotensive response was significantly inhibited by the nitric oxide synthase inhibitor, N(G)-nitro-l-arginine methyl ester (L-NAME, 100 mg kg(-1) intraperitoneally [ip]) only in Con rats. Clofibrate (Clof, 200 mg kg(-1) ip) did not change blood pressure but increased ACh-induced hypotensive responses only in Sal, an effect that was abolished by subsequent administration of apamin (Apa, 50 microg kg(-1) iv) and charybdotoxin (ChTx, 50 microg kg(-1) iv). Apa+ChTx blocked responses to ACh in Con and Sal, as expected. A single dose of clofibrate (200 mg kg(-1) ip), given subsequently to Apa+ChTx, restored responses to ACh in both the Con and Sal groups, again without affecting baseline MAP. CONCLUSION: Clofibrate has an acute salutary effect on endothelium-dependent vasodilation in saline-treated rats, probably mediated through vascular calcium-activated potassium channels and independent of an antihypertensive effect.  相似文献   
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Endothelial dysfunction of the maternal vasculature induced by pro-oxidants may contribute to the development of preeclampsia. Obesity results in vascular inflammation and oxidative stress and is therefore a risk factor for preeclampsia. Regular exercise is known to induce antioxidants. We recently demonstrated that stretchers (subjects who performed low-intensity exercises) had a lower incidence of preeclampsia as opposed to walkers (moderate-intensity exercise; 2.6% versus 14.6%). We now seek to determine the possible protective mechanisms. We hypothesized that stretchers will have higher vascular levels of the antioxidant superoxide dismutase (SOD) and plasma transferrin levels, an antioxidant marker. We conducted immunohistochemical analyses of blood vessels embedded in fat biopsy samples obtained during cesarean sections from women who were randomized to either stretching ( N?=?6) or walking ( N?=?5) exercises. In addition, levels of plasma transferrin were measured. SOD expression was increased ( P?相似文献   
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