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Notes: 1. In the present study, we used a low dose of propofol (5 mg/kg per h) to investigate its effects on the pro-inflammatory cytokines (tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10) and changes in nitric oxide (NO) following lipopolysaccharide (LPS) for a period of 12 h in conscious rats.2. Experiments were designed to induce endotoxin shock by intravenous injection of Klebsiella pneumoniae LPS (10 mg/kg) in conscious rats. Arterial pressure (AP) and heart rate (HR) were monitored continuously for 12 h after LPS administration. Tumour necrosis factor-α, IL-1β, IL-10 and plasma nitrates/nitrites were determined before and 0.5, 1, 3, 6, 9 and 12 h after LPS administration. A low dose of intravenous propofol (5 mg/kg per h) was administered to investigate the effects on cytokine responses and changes in NO in endotoxin shock.3. Lipopolysaccharide significantly increased TNF-α, IL-1β, IL-10, nitrites/nitrates and HR, whereas mean AP was decreased. Post-treatment with propofol suppressed the release of TNF-α, IL-1β, IL-10 and NO production after endotoxin shock.4. Lipopolysaccharide also caused a decrease in the white blood cell count and haematocrit.5. Post-treatment with propofol slightly, but not significantly, affected the LPS-induced systemic hypotension, tachycardia, leukocytopenia and anaemia.6. These findings suggest that low-dose propofol may be beneficial to the inflammatory change in sepsis.

Notes: 1. Nitric oxide (NO) plays an important role in various physiological functions. The continuous formation of endogenous NO from endothelial cells maintains a vasodilator tone and regulates blood flow and pressure. However, the role of NO in hypertension remains controversial.2. In the present study, we used an in situ mesenteric perfusion system. The primary objectives of the study were to examine whether or not mesenteric vasoreactivity is changed by alterations in perfusion pressure and to assess the role of NO in changes of vascular reactivity in hypertension.3. Spontaneously hypertensive rats (SHR; 12–15 weeks of age) and age-matched normotensive Wistar-Kyoto (WKY) rats were used as the experimental and control groups, respectively. Endothelium-dependent and -independent vasodilation was detected by acetylcholine (ACh) or NO donors (sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP)). Dose-dependent reactivity to these agents (10–6 to 10–4 mol/L) was detected by bolus intra-arterial injections of 10 μL of the test agents at 5 min intervals. Dose-dependent responses to vasoconstrictor drugs, such as noradrenaline (NA) and phenylephrine (PE; 10–6 to 10–4 mol/L) were also observed. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg) was given to examine the contribution of NO to the vasoreactivity of the mesenteric bed.4. Acetylcholine, SNP and SNAP produced dose-dependent vasodilation in both WKY rats and SHR. The magnitude of the vasodilation was significantly greater in SHR than in WKY rats. It was also greater at high than low flow rates in SHR. The increase in mesenteric perfusion pressure following L-NAME was significantly higher in SHR than in WKY rats. However, there were no differences in responses to L-NAME between low and high flow rates in SHR. Endothelium-independent vasoconstriction (NA and PE) was dose dependent in both SHR and WKY rats. The magnitude of the endothelium-independent vasoconstriction was greater in SHR than in WKY rats.5. The results suggest that endothelium-dependent or -independent mesenteric vasoconstriction and vasodilation is enhanced in SHR compared with WKY rats, supporting the concept of enhancement of NO function in the hypertensive state. Flow-induced shear stress is also a key factor in the regulation of peripheral resistance depending on NO formation in hypertension.

Notes: 1. The present study was undertaken to determine the locus of nitric oxide (NO) production that is toxic to the lung and produces acute pulmonary oedema in endotoxin shock, to examine and compare the effects of changes in lung perfusate on endotoxin-induced pulmonary oedema (EPE) and to evaluate the involvement of constitutive and inducible NO synthase (cNOS and iNOS, respectively).2. Experiments were designed to induce septic shock in anaesthetized rats with the administration of Escherichia coli lipopolysaccharide (LPS). Exhaled NO, lung weight (LW)/bodyweight (BW) ratio, LW gain (LWG) and lung histology were measured and observed to determine the degree of EPE 4 h following LPS. The EPE was compared between groups in which LPS had been injected either into the systemic circulation or into the isolated perfused lung. The lung perfusate was altered from whole blood to physiological saline solution (PSS) with 6% albumin to test whether different lung perfusions affected EPE. Pretreatment with various NOS inhibitors was undertaken 10 min before LPS to investigate the contribution of cNOS and iNOS to the observed effects.3. Endotoxin caused profound systemic hypotension, but little change in pulmonary arterial pressure. The extent of EPE was not different between that induced by systemic injection and that following administration to isolated lungs preparations. Replacement of whole blood with PSS greatly attenuated (P 〈 0.05) EPE. In blood-perfused lungs, pretreatment with NOS inhibitors, such as Nω-nitro-L-arginine methyl ester, aminoguanidine and dexamethasone, significantly prevented EPE (P 〈 0.05).4. The major site of NO production through the whole blood is in the lung. The NO production mediated by the iNOS system is toxic to the endothelium in the pulmonary microvasculature. Inhalation of NO for patients with sepsis may be used with clinical caution. Therapeutic consideration of lung extracorporeal perfusion with PSS and pharmacological pretreatment with iNOS inhibitors may be warranted.