Decrease In Nitric Oxide Metabolites Research Articles

Decreased serum L-arginine and L-citrulline levels in major depression.

It has been suggested that endothelial dysfunction caused by a decreased endothelial production of nitric oxide (NO) may contribute to the consistently observed increased risk of developing cardiovascular disease (CVD) in physically healthy patients suffering from major depression (MD). NO is a gas synthesized from Larginine (a conditionally essential amino acid) and oxygen by endothelial nitric oxide synthase (eNOS). The end products of NO production include both NO and L-citrulline. NO is rapidly reduced to the anions nitrite and nitrate, classically referred to as NO metabolites. Their measurement has been used as a surrogate measurement for endothelial NO production. We and others have shown decreased levels of NO metabolites in the serum of MD patients. The mechanism of this decreased production of NO by the endothelium has not yet been elucidated. The purpose of this study is to assess serum levels of L-arginine and L-citrulline in patients with MD. Levels of L-arginine and L-citrulline were measured in 35 unmedicated physically healthy MD patients and 36 healthy controls (HCs). L-arginine and L-citrulline concentrations were significantly lower in MD patients than in healthy controls (L-arginine, 73.54+21.53μmol/L and 84.89+25.16, p=0.04μmol/L and L-citrulline 31.58+6.05μmol/L and 35.19+6.85μmol/L, p=0.03, respectively). The decrease in L-arginine levels in MD patients is a possible explanation for the decrease in NO metabolites in MD patients and therefore may contribute, through endothelial dysfunction, to the increased CV risk associated with MD.

Cyclooxygenase-2 Inhibition Limits Angiotensin II-Induced DNA Oxidation and Protein Nitration in Humans.

Compared to other cyclooxygenase-2 inhibitors, celecoxib is associated with a lower cardiovascular risk, though the mechanism remains unclear. Angiotensin II is an important mediator of oxidative stress in the pathophysiology of vascular disease. Cyclooxygenase-2 may modify the effects of angiotensin II though this has never been studied in humans. The purpose of the study was to test the effects of selective cyclooxygenase-2 inhibition on plasma measures of oxidative stress, the vasoconstrictor endothelin-1, and nitric oxide metabolites, both at baseline and in respose to Angiotensin II challenge in healthy humans. Measures of 8-hydroxydeoxyguanosine, advanced oxidation protein products, nitrotyrosine, endothelin-1, and nitric oxide metabolites were assessed from plasma samples drawn at baseline and in response to graded angiotensin II infusion (3 ng/kg/min × 30 min, 6 ng/kg/min × 30 min) before and after 14 days of cyclooxygenase-2 inhibition in 14 healthy subjects (eight male, six female) in high salt balance, a state of maximal renin angiotensin system suppression. Angiotensin II infusion significantly increased plasma oxidative stress compared to baseline (8-hydroxydeoxyguanosine; +17%; advanced oxidation protein products; +16%), nitrotyrosine (+76%). Furthermore, levels of endothelin-1 levels were significantly increased (+115%) and nitric oxide metabolites were significantly decreased (−20%). Cycloxygenase-2 inhibition significantly limited the increase in 8-hydroxydeoxyguanosine, nitrotyrosine and the decrease in nitric oxide metabolites induced by angiotensin II infusion, though no changes in advanced oxidation protein products and endothelin-1 concentrations were observed. Cyclooxygenase-2 inhibition with celecoxib partially limited the angiotensin II-mediated increases in markers of oxidative stress in humans, offering a potential physiological pathway for the improved cardiovascular risk profile of this drug.

The Impact of Surgery and Stored Red Blood Cell Transfusions on Nitric Oxide Homeostasis.

Cell-free hemoglobin (Hb) forms in stored red blood cells (RBCs) as a result of hemolysis. Studies suggest that this cell-free Hb may decrease nitric oxide (NO) bioavailability, potentially leading to endothelial dysfunction, vascular injury, and multiorgan dysfunction after transfusion. We tested the hypothesis that moderate doses of stored RBC transfusions increase cell-free Hb and decrease NO availability in postoperative surgical patients. Twenty-six patients undergoing multilevel spine fusion surgery were studied. We compared those who received no stored RBCs (n = 9) with those who received moderate amounts (6.1 ± 3.0 units) of stored RBCs over 3 perioperative days (n = 17). Percent hemolysis (cell-free Hb), RBC-NO (heme-NO), and plasma nitrite and nitrate were measured in samples from the stored RBC bags and from patients' blood, before and after surgery. Posttransfusion hemolysis was increased approximately 3.5-fold over preoperative levels (P = 0.0002) in blood samples collected immediately after surgery but not on postoperative days 1 to 3. Decreases in both heme-NO (by approximately 50%) and plasma nitrite (by approximately 40%) occurred postoperatively, both in nontransfused patients (P = 0.036 and P = 0.026, respectively) and transfused patients (P = 0.0068 and P = 0.003, respectively) and returned to preoperative baseline levels by postoperative day 2 or 3. Postoperative plasma nitrite and nitrate were decreased significantly in both groups, and this change was slower to return to baseline in the transfused patients, suggesting that blood loss and hemodilution from crystalloid administration contribute to this finding. The decrease in NO metabolites occurred irrespective of stored RBC transfusions, suggesting this decrease may be related to blood loss during surgery and hemodilution rather than to scavenging of NO or inhibition of NO synthesis by stored RBC transfusions.

Determinants of outcome for patients undergoing lumbar discectomy: a pilot study

One-third of patients who undergo lumbar discectomy continue to suffer from persistent pain postoperatively. Greater preoperative warmth thresholds and greater preoperative cerebrospinal fluid concentrations of stable serum nitric oxide metabolites are associated with a worse outcome. The principal objective of this study was to examine the relationship between patient outcome (defined using the Modified Stauffer-Coventry evaluating criteria) and preoperative pain perception threshold to an electrical stimulus. A prospective observational pilot study of patients (n = 39) was performed. Quantitative sensory testing, visual analogue scales for anxiety and pain, the Hospital Anxiety and Depression (HADS) Scale and the McGill Pain Questionnaire were completed, and serum nitric oxide metabolites were measured perioperatively. Excised disc tissue was examined histologically, and immunohistochemistry for phospholipase A2 was performed. Ten patients (26%) had an unsatisfactory outcome. Those with a satisfactory outcome had greater preoperative pain perception thresholds over the affected dermatome, which decreased by 2 months postoperatively. These patients also demonstrated a decrease in nitric oxide metabolites from preoperatively to 18 h postoperatively. Greater preoperative HADS scores, and greater pain intensity 4 h and 24 h postoperatively were associated with an unsatisfactory outcome. Patients with a satisfactory outcome demonstrate a decrease in pain perception thresholds and plasma concentration of stable nitric oxide metabolites during the perioperative period. Patients with an unsatisfactory outcome following lumbar discectomy experience greater preoperative anxiety and greater pain during the early postoperative period. These findings justify a larger prospective observational study.

Serum levels of nitric oxide metabolites during labour with or without combined spinal-epidural analgesia

Combined spinal-epidural analgesia is effective in labour analgesia. Nitric oxide may play important roles in pregnancy and labour and is probably affected by labour pain. The aim of the present study was to explore the alteration in serum levels of nitric oxide metabolites, i.e. nitrate and nitrite, during labour with or without combined spinal-epidural analgesia. Fifty pregnant women were recruited at the cervical dilatation of 3 approximately 4 cm, 25 received combined spinal-epidural analgesia and 25 served as control. Twenty in the combined spinal-epidural analgesia group and 19 in the control group finished data collection and were included in the analysis. Blood samples were taken at study entry, full cervical dilation and 2 h after delivery. Total serum level of nitrite and nitrate was measured with enzymatic conversion and followed by Griess reaction. Visual analogue pain scores and mean blood pressure were monitored. After analgesia, pain score and mean blood pressure were significantly lower in the combined spinal-epidural analgesia group than in the control group (P 0.05) but significantly different at full cervical dilation and 2 h after delivery (P 0.05). Combined spinal-epidural analgesia provided effective analgesia and abolished the decrease in nitric oxide metabolites during active labour.

Antihypertensive Effect of Quercetin in Rats Fed with a High-Fat High-Sucrose Diet

The effects of different levels of quercetin on the blood pressure were studied in 6-week-old male Sprague-Dawley rats. The rats were fed with a control diet or a high-fat high-sucrose (HFS) diet containing 0, 0.02, 0.07, 0.2, or 0.5% quercetin for 4 weeks. The systolic blood pressure and the lipid peroxides in the plasma were both higher in the rats fed with the HFS diet without quercetin than in the rats fed with the control diet. The nitric oxide synthase (NOS) activity in the vascular tissues and nitric oxide (NO) metabolites in the plasma and urine were both lower in these rats. A distinct depression of the increase in blood pressure was found in the rats fed with the HFS diets containing quercetin. Each level of quercetin examined was effective, the 0.5% level being much more effective than other levels. Dietary quercetin decreased lipid peroxidation in the plasma of the rats fed with the HFS diets. Quercetin also suppressed the decrease in NO metabolites in the plasma and urine, and the NOS activity in the vascular tissues of these rats. These results suggest that the increased NO availability caused by the elevated NOS activity, and the antioxidative activity in these rats fed with quercetin may be sources of the antihypertensive effect of quercetin.

Isoflurane-sevoflurane adminstration before ischemia attenuates ischemia-reperfusion-induced injury in isolated rat lungs.

The effects of volatile anesthetics on ischemia-reperfusion (IR)-induced lung injury are not clear. The authors investigated the effects of preadministration of isoflurane and sevoflurane on IR-induced lung injury in an isolated buffer-perfused rat lung model. Isolated rat lungs were designated into four groups: control group (n = 6): perfusion for 120 min without ischemia; IR group (n = 6): interruption of perfusion and ventilation for 60 min followed by reperfusion for 60 min; sevoflurane (SEVO)-IR (n = 6) and isoflurane (ISO)-IR (n = 6) groups: 1 minimum alveolar concentration (MAC) isoflurane or sevoflurane was administered for 30 min, followed by 60 min ischemia, then 60 min reperfusion. The authors measured the coefficient of filtration (Kfc) of the lung, lactate dehydrogenase (LDH) activity, tumor necrosis factor alpha, and nitric oxide metabolites (nitrite + nitrate) in the perfusate and the wet-to-dry lung weight ratio. IR caused significant increases in the coefficient of filtration (approximately sevenfold at 60 min of reperfusion compared with baseline; P < 0.01), the wet-to-dry lung weight ratio, the rate of increase of lactate dehydrogenase activity, and tumor necrosis factor a in the perfusate, and caused a significant decrease in nitric oxide metabolites in the perfusate. Administration of 1 MAC isoflurane or sevoflurane before ischemia significantly attenuated IR-induced increases in the coefficient of filtration and the wet-to-dry lung weight ratio, inhibited increases in the rate of increase of lactate dehydrogenase activity and tumor necrosis factor alpha in the perfusate, and abrogated the decrease in nitric oxide metabolites in the perfusate. No difference was found between the SEVO-IR and ISO-IR groups. Isoflurane and sevoflurane administered before ischemia can attenuate IR-induced injury in isolated rat lungs.