Animals ; Cardiovascular Diseases ; drug therapy ; etiology ; Creatine Kinase, MB Form ; blood ; Heart ; drug effects ; Interleukin-1 ; blood ; Interleukin-6 ; blood ; Lycium ; chemistry ; Male ; Nitrates ; blood ; Oxidative Stress ; drug effects ; Physical Conditioning, Animal ; adverse effects ; Plant Extracts ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; blood

OBJECTIVEThe present study investigated the protective role of Hyparrhenia hirta (H. hirta) against sodium nitrate (NaNO3)-induced hepatoxicity.

METHODSMale Wistar rats were randomly divided into three groups: a control group and two treated groups during 50 d with NaNO3 administered either alone in drinking water or co-administered with H. hirta.

RESULTSNaNO3 treatment induced a significant increase in serum levels of glucose, total cholesterol and triglyceride while serum total protein level decreased significantly. Transaminases and lactate deshydrogenase activities in serum were elevated indicating hepatic cells' damage after treatment with NaNO3. The hyperbilirubinemia and the increased serum gamma glutamyl transferase activities suggested the presence of cholestasis in NaNO3 exposed rats. In parallel, a significant increase in malondialdehyde level along with a concomitant decrease in total glutathione content and superoxide dismutase, catalase and glutathione peroxidase activities were observed in the liver after NaNO3 treatment. Furthermore, nitrate caused a significant induction of DNA fragmentation. These modifications in NaNO3-treated rats corresponded histologically with hepatocellular necrosis and mononuclear cells infiltration. H. hirta supplementation showed a remarkable amelioration of the abnormalities cited above.

CONCLUSIONThe results concluded that the treatment with H. hirta had a significant role in protecting the animals from nitrate-induced liver dysfunction.

Animals ; Chemical and Drug Induced Liver Injury ; prevention & control ; DNA Fragmentation ; drug effects ; Drug Evaluation, Preclinical ; Eating ; drug effects ; Flavonoids ; analysis ; Glutathione ; drug effects ; Lipid Peroxidation ; drug effects ; Lipids ; blood ; Liver ; drug effects ; metabolism ; pathology ; Male ; Mice ; Nitrates ; Organ Size ; drug effects ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Poaceae ; chemistry ; Random Allocation ; Rats, Wistar

BACKGROUNDSalivary nitrate is positively correlated with plasma nitrate and its level is 9 times the plasma level after nitrate loading. Nitrate in saliva is known to be reduced to nitrite by oral bacteria. Nitrate and nitrite levels in saliva are 3 - 5 times those in serum in physiological conditions respectively in our previous study. The biological functions of high salivary nitrate and nitrite are still not well understood. The aim of this in vitro study was to investigate the antimicrobial effects of nitrate and nitrite on main oral pathogens under acidic conditions.

METHODSSix common oral pathogens including Streptococcus mutans NCTC 10449, Lactobacillus acidophilus ATCC 4646, Porphyromonas gingivalis ATCC 33277, Capnocytophaga gingivalis ATCC 33624, Fusobacterium nucleatum ATCC 10953, and Candida albicans ATCC 10231 were cultured in liquid medium. Sodium nitrate or sodium nitrite was added to the medium to final concentrations of 0, 0.5, 1, 2, and 10 mmol/L. All of the microorganisms were incubated for 24 to 48 hours. The optical densities (OD) of cell suspensions were determined and the cultures were transferred to solid nutrient broth medium to observe the minimum inhibitory concentration and minimum bactericidal/fungicidal concentration for the six tested pathogens.

RESULTSNitrite at concentrations of 0.5 to 10 mmol/L had an inhibitory effect on all tested organisms at low pH values. The antimicrobial effect of nitrite increased with the acidity of the medium. Streptococcus mutans NCTC 10449 was highly sensitive to nitrite at low pH values. Lactobacillus acidophilus ATCC 4646 and Candida albicans ATCC 10231 were relatively resistant to acidified nitrite. Nitrate at the given concentrations and under acidic conditions had no inhibitory effect on the growth of any of the tested pathogens.

CONCLUSIONNitrite, at a concentration equal to that in human saliva, is both cytocidal and cytostatic to six principal oral pathogens in vitro, whereas nitrate at a similar concentration has no antimicrobial effect on these organisms.

Anti-Infective Agents ; pharmacology ; Candida albicans ; drug effects ; Fusobacterium nucleatum ; drug effects ; Hydrogen-Ion Concentration ; Lactobacillus acidophilus ; drug effects ; Microbial Sensitivity Tests ; Mouth ; microbiology ; Nitrates ; analysis ; blood ; pharmacology ; Nitrites ; analysis ; blood ; pharmacology ; Porphyromonas gingivalis ; drug effects ; Saliva ; chemistry ; Streptococcus mutans ; drug effects

The monitoring of airway inflammation has assessed in bronchial asthma directly by sputum examination, and indirectly by measurements in peripheral blood. To investigate the diagnostic value of these two methods, we compared nitric oxide (NO) metabolites, eosinophils, and eosinophil cationic protein (ECP) in sputum and blood in patients with asthma and control subjects. Sputum and serum were obtained from fifteen patients with asthma, and then were examined before anti-asthma treatment, including steroid preparations. ECP was measured by fluoroimmunoassay. NO metabolites were assayed by using modified Griess reaction. Asthmatic patients, compared with control subjects, had significantly higher level of NO metabolites, higher proportion of eosinophils, and higher levels of ECP in sputum. Asthmatic patients, compared with control subjects, however, had significantly higher number of eosinophils, and were at higher levels of ECP in blood. FEV1, FEV1 /FVC was negatively correlated with sputum eosinophils. The area under receiver operating characteristic(ROC) curve showed that eosinophils in sputum are significantly accurate markers than NO metabolites in sputum and blood. These findings suggest that the proportion of eosinophils in sputum have more accurate diagnostic marker of asthmatic airway inflammation than NO metabolites in sputum in differentiating asthmatic patients from control subjects.
Adult ; Area Under Curve ; Asthma/*blood/*metabolism ; Blood Proteins/*metabolism ; Comparative Study ; Eosinophils/*metabolism ; Female ; Fluoroimmunoassay ; Human ; Inflammation ; Male ; Nitrates/metabolism ; Nitric Oxide/blood/*metabolism ; Nitrites/metabolism ; ROC Curve ; Ribonucleases/blood/*metabolism ; Sputum/*metabolism

BACKGROUND AND OBJECTIVES: Coronary flow reserve (CFR) is the capability of coronary arteriolar bed to dilate in response to increased cardiac metabolic demand. Nocorandil, a hybrid of ATP-sensitive K+ channel opener and nitrates, causes coronary vasodilation of both epicardial and resistance vessels. We investigated the feasibility and safety of nicorandil as compared to adenosine in the measurement of CFR using a Doppler guide wire. SUBJECTS AND METHODS: We measured CFR in 26 consecutive patients (mean age 52+/-19 years, M:F=16:10) during coronary intervention with a 0.014-inch Doppler guide wire. We recorded the baseline average peak velocity (APV) and the hyperemic APV induced by intracoronary adenosine or nicorandil. The heart rate, mean aortic pressure and the time interval from maximal APV to baseline APV were also recorded. RESULTS: There were no significant differences between APV, diastole/systole velocity ratio and CFR induced by adenosine and those induced by nicorandil (44.4 +/- 17.3 vs 45.5 +/- 17.6, p=0.78, 1.59 +/- 0.51 vs 1.57 +/- 0.52 p=0.78, 2.22 +/- 0.89 vs 2.27 +/- 0.94, p=0.36). The CFR and diastole/systole velocity ratio induced by nicorandil showed a strong positive linear correlation with those by adenosine (r2=0.77, p=0.0001, r2=0.83, p=0.0001). Adenosine significantly decreased the heart rate as compared to nicorandil =-25.5 +/- 9.7 vs -8.7 +/- 4.9 bpm, p=0.001). There were no differences in the changes of mean aortic pressure between adenosine and nicorandil (-7 +/- 9 vs -2 +/- 3 mmHg, p=0.17). Nicorandil prolonged the time interval from maximal APV to baseline APV compared to adenosine (194 +/- 62 vs 37 +/- 12 sec, p=0.001). CONCLUSION: Nicorandil is feasible and safe for use in measuring CFR using a Doppler guide wire and may replace adenosine.
Adenosine* ; Arterial Pressure ; Blood Flow Velocity ; Heart Rate ; Humans ; Nicorandil* ; Nitrates ; Ultrasonography ; Vasodilation

OBJECTIVETo observe the effect of nitric oxide (NO) on the survival of a random pattern skin flap.

METHODSCaudal based random skin flaps (9 cm x 3 cm) were raised on the back of Wistar rats. Six methods were used in the experiment to observe the effect of NO synthase inhibitor L-NAME and NO synthase substrate L-arginine on flaps: image analysis technology; light and electron microscopic studies; enzyme histochemistry of NOS in flaps; concentration of NO2-/NO3- in plasma and wet/dry ratio of the flap tissue.

RESULTSSurvival area of flap in the L-arginine-treated group significantly increased (67.06 +/- 5.65)% (p < 0.01) whereas the area in the L-NAME-treated group significantly decreased (35.17 +/- 1.87)% (p < 0.01) compared with the control group (53.25 +/- 3.24)% at seven days after the operation. General and microscopic observations showed that pathological changes in the L-arginine-treated group were fewer. Abundant capillaries and fewer inflammatory cells were noticed in the L-arginine-treated group. Transmission Electron Microscopy (TEM) studies find endothelial swelling, thrombosis-formation and endothelial loss of contact with the basement membrane in the L-NAME treated group. Before operation, the serum NO concentrations were not significantly different in three groups (p > 0.05). After operation, NO concentration of the control group began to increase and reached to the top at the third day. L-Arg kept serum NO concentration in a higher level than the control. Enzyme histochemistry of NOS in flaps: microvessel intima in dermis, hair follicles, sweat glands and inflammatory cells showed oxford blue, more positive in flaps of the L-Arg treated group than the control group at the third day after operation. The flaps of L-NAME-treated group demonstrated negative or weak positive. Wet/dry ratio: twenty-four hours after flap elevation wet/dry weight ratios increased significantly in all regions of the flap of the L-arginine-treated rats compared with saline-treated rats. The ratios of the flaps of L-NAME-treated rats were reduced compared with saline-treated rats.

CONCLUSIONNO could improve microcirculation of the flap and increase its survival rates. The mechanism might be that NO could accelerate flap vascularization and protect flaps from ischemia-reperfusion injury.

Animals ; Arginine ; pharmacology ; Dermatologic Surgical Procedures ; Enzyme Inhibitors ; pharmacology ; Female ; Graft Survival ; drug effects ; Immunohistochemistry ; Male ; Microscopy, Electron ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitrates ; blood ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; antagonists & inhibitors ; metabolism ; Nitrites ; blood ; Rats ; Rats, Wistar ; Skin ; enzymology ; ultrastructure ; Skin Transplantation ; Surgical Flaps ; physiology

BACKGROUND AND OBJECTIVES: The clinical efficacy of transdermal nitroglycerin patch in patients with angina has not known exactly. After the application of transdermal nitroglycerin, the influences of transdermal nitrate on exercise capacity and clinical symptom in patients with angina were compared with the clinical effects of oral nitroglycerin. MATERIALS AND METHOD: Long acting oral nitrate was administered in 20 patients (9 male, 11 female, age:56.3+/-4.6) and transdermal nitrate (Angiderm Patch ) applied in 20 patients (8 male, 12 female, age:53.9+/-9.8), who suffered from angina more than 4 attacks per week. All patients were evaluated at 4-week interval:after 2 weeks' run-in period, after 4 weeks of randomized non-titrated treatment (first visit), after 8 and 12 weeks of titrated treatment (second and third visits). The frequency of angina, side effects of headache and skin irritation, blood pressure, echocardiographic ejection fraction and exercise treadmill score were compared between the two groups. RESULTS: The frequency of angina attack was 14.4+/-6.0 in oral nitrate and 14.0+/-4.9 in transdermal nitrate per two weeks during run-in period. After nitrates, the frequency of angina reduced to 8.1+/-4.5, 5.4+/-2.2 on the first, to 3.0+/-3.5 and 1.7+/-1.4 on the second, and to 1.2+/-1.7 and 0.3+/-0.4 on the third visit in oral and transdermal nitrate groups respectively. Blood pressure and ejection fraction were unchanged in both groups. Exercise treadmill score was 10.4+/-4.3 in oral and 10.6+/-2.3 in transdermal nitrate group during run-in period, which was increased to 12.6+/-4.0, 13.7+/-2.5 on the first, to 13.6+/-3.0, 15.1+/-2.2 on the second, and to 15.3+/-2.7, 15.6+/-1.9 on the third visit after oral and transdermal nitrates respectively. However, changes in the frequency of anginal episodes and exercise treadmill score were not different between two groups. Side effects of headache were observed in 7 of oral and 4 of transdermal nitrate group and skin irritation in 2 of transdermal group. CONCLUSION: Transdermal nitroglycerin is equally effective as oral nitroglycerin in the reduction of the frequency of angina attack and the improvement of exercise tolerance without significant side effects in patients with angina.
Blood Pressure ; Echocardiography ; Exercise Tolerance ; Female ; Headache ; Humans ; Male ; Nitrates ; Nitroglycerin ; Skin

We investigated to see whether an altered role of nitric oxide (NO) system is involved in erythropoietin (EPO)-induced hypertension in chronic renal failure (CRF). Male Sprague-Dawley rats were five-sixths nephrectomized to induce CRF. Six weeks after the operation, EPO or vehicle was injected for another 6 weeks. Plasma and urine nitrite/nitrate (NOx) levels were determined. Expression of NO synthase (NOS) proteins in the aortae and kidneys were also determined. In addition, the isometric tension of isolated aorta in response to acetylcholine and nitroprusside was examined. Blood pressure progressively rose in CRF groups, the degree of which was augmented by EPO treatment. Plasma NOx levels did not differ among the groups, while urine NOx levels were lower in CRF groups. Endothelial NOS expression was lower in the kidney and aorta in CRF rats, which was not further affected by EPO-treatment. The inducible NOS expression in the kidney and aorta was not different among the groups. Acetylcholine and sodium nitroprusside caused dose-dependent relaxations of aortic rings, the degree of which was not altered by EPO-treatment. Taken together, EPO-treatment aggravates hypertension in CRF, but altered role of NO system may not be involved.
Acetylcholine/pharmacology ; Anemia/metabolism ; Anemia/etiology ; Anemia/drug therapy* ; Animal ; Aorta, Thoracic/physiology ; Body Weight ; Erythropoietin/pharmacology* ; Hypertension, Renal/metabolism ; Hypertension, Renal/drug therapy ; Isometric Contraction/drug effects ; Kidney/enzymology ; Kidney Failure, Chronic/metabolism* ; Kidney Failure, Chronic/complications ; Male ; Nitrates/urine ; Nitrates/blood ; Nitric Oxide/metabolism* ; Nitric-Oxide Synthase/metabolism ; Nitrites/urine ; Nitrites/blood ; Nitroprusside/pharmacology ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction/drug effects ; Vasoconstrictor Agents/pharmacology ; Vasodilator Agents/pharmacology

The present study was aimed at investigating whether an altered role of nitric oxide (NO) is involved in chronic renal failure (CRF). Rats were subjected to 5/6 nephrectomy and kept for 6 weeks to induce CRF. On the experimental day, after measurement of arterial pressure under anesthesia, the arterial blood was collected, and thoracic aorta and kidney were rapidly taken. NO metabolites (NOx) were determined in the plasma, urine, aorta and kidney. The expression of NO synthase (NOS) isozymes was determined in the kidney and aorta by Western blot analysis. The expression of NOS mRNA in the glomeruli was also determined by RT-PCR. There were significant increases in arterial pressure and serum creatinine levels in CRF. Urine NOx levels were decreased in CRF, whereas plasma NOx levels were not altered. Aorta and kidney tissue NOx levels were also decreased in CRF. The expression of endothelial constitutive (ec) and inducible (i) isoforms of NOS proteins was decreased in the kidney and aorta in CRF. Accordingly, the expression of ecNOS and iNOS mRNA was decreased in the glomeruli in CRF. In conclusion, NO synthesis is decreased in the kidney and vasculature of CRF rats.
Animal ; Aorta, Thoracic/metabolism ; Comparative Study ; Enzyme Induction ; Isoenzymes/metabolism+ACo- ; Isoenzymes/genetics ; Kidney/metabolism ; Kidney Failure, Chronic/metabolism+ACo- ; Male ; Nephrectomy ; Nitrates/urine ; Nitrates/blood ; Nitric Oxide/deficiency+ACo- ; Nitric Oxide/biosynthesis ; Nitric-Oxide Synthase/metabolism+ACo- ; Nitric-Oxide Synthase/genetics ; Nitrites/urine ; Nitrites/blood ; Organ Specificity ; RNA, Messenger/biosynthesis ; Rats ; Rats, Sprague-Dawley

The present study was aimed at investigating whether an altered role of nitric oxide (NO) is involved in chronic renal failure (CRF). Rats were subjected to 5/6 nephrectomy and kept for 6 weeks to induce CRF. On the experimental day, after measurement of arterial pressure under anesthesia, the arterial blood was collected, and thoracic aorta and kidney were rapidly taken. NO metabolites (NOx) were determined in the plasma, urine, aorta and kidney. The expression of NO synthase (NOS) isozymes was determined in the kidney and aorta by Western blot analysis. The expression of NOS mRNA in the glomeruli was also determined by RT-PCR. There were significant increases in arterial pressure and serum creatinine levels in CRF. Urine NOx levels were decreased in CRF, whereas plasma NOx levels were not altered. Aorta and kidney tissue NOx levels were also decreased in CRF. The expression of endothelial constitutive (ec) and inducible (i) isoforms of NOS proteins was decreased in the kidney and aorta in CRF. Accordingly, the expression of ecNOS and iNOS mRNA was decreased in the glomeruli in CRF. In conclusion, NO synthesis is decreased in the kidney and vasculature of CRF rats.
Animal ; Aorta, Thoracic/metabolism ; Comparative Study ; Enzyme Induction ; Isoenzymes/metabolism+ACo- ; Isoenzymes/genetics ; Kidney/metabolism ; Kidney Failure, Chronic/metabolism+ACo- ; Male ; Nephrectomy ; Nitrates/urine ; Nitrates/blood ; Nitric Oxide/deficiency+ACo- ; Nitric Oxide/biosynthesis ; Nitric-Oxide Synthase/metabolism+ACo- ; Nitric-Oxide Synthase/genetics ; Nitrites/urine ; Nitrites/blood ; Organ Specificity ; RNA, Messenger/biosynthesis ; Rats ; Rats, Sprague-Dawley