The preventive effects of nitroglycerine (NG) on glucocorticoid-induced osteoporosis in growing rats were studied. Three-month-old female Wistar rats were randomly divided into control group (CON), dexamethasone group (DXM), DXM plus a low dose NG group (NG-L), DXM plus a middle dose NG group (NG-M) and DXM plus a high dose NG group (NG-H), 8 rats in each group. The rat model of osteoporosis was developed by intramuscular injection of dexamethasone twice a week. NG 0.2, 0.4 and 1.0 mg/kg was administered by oral gavages to the treatment groups every day for 12 weeks. Rats in CON group and DXM group were treated with normal saline of the same amount. After the treatment, the bone mineral density (BMD) and bone metabolism-associated biochemical markers were determined. Compared with CON group, BMD of lumbar spine and femur in DXM group was decreased significantly (P<0.05 and P<0.01 respectively), blood BGP levels and NO levels reduced (both P<0.01), and TRAP level increased (P<0.05). As compared with DXM group, BMD, serum BGP and NO were increased, and TRAP decreased in NG-L group and NG-M group, but had no significant difference in comparison to CON group. All the markers other than serum NO and TRAP levels had no significant difference between NG-H group and DXM group. It was concluded that low or middle doses of NG could prevent glucocorticoid-induced bone loss in growing rats, but high dose of NG could not. Supplement with NO donor could be considered as a preventive treatment for glucocorticoid-induced osteoporosis in a developing skeleton.
Bone Density/*drug effects ; Dexamethasone ; Nitric Oxide Donors/*therapeutic use ; Nitroglycerin/pharmacology ; Nitroglycerin/*therapeutic use ; Osteoporosis/chemically induced ; Osteoporosis/*prevention & control ; Random Allocation ; Rats, Wistar

Administration, Inhalation ; Endothelium-Dependent Relaxing Factors ; pharmacology ; Humans ; Hypertension, Pulmonary ; drug therapy ; Nitric Oxide Donors ; administration & dosage ; therapeutic use ; Nitroglycerin ; administration & dosage ; therapeutic use ; Nitroprusside ; administration & dosage ; therapeutic use ; Phosphodiesterase Inhibitors ; administration & dosage ; therapeutic use

Nitric oxide (NO) as a messenger and/or effector plays important roles in vivo. The decreased availability of NO or dysfunction in NO signaling has often been implicated in the development and progression of diseases, and design and research of NO-donating drugs has become one of the important strategies in drug discovery. In connection with authors' scientific practice, this article reviews the recent advances in the research of NO-donating drugs.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Aspirin ; analogs & derivatives ; pharmacology ; therapeutic use ; Azo Compounds ; pharmacology ; Cardiovascular Diseases ; drug therapy ; Cell Line, Tumor ; Drug Design ; Humans ; Neoplasms ; drug therapy ; pathology ; Nitrates ; pharmacology ; therapeutic use ; Nitric Oxide ; metabolism ; Nitric Oxide Donors ; pharmacology ; therapeutic use ; Piperazines ; pharmacology ; Signal Transduction ; drug effects

AIMTo search for novel antiasthmatic agents.

METHODSCoupling seratrodast (SD), an antiasthmatic drug, with several different types of NO donors including oxatriazoles, N-hydroxyguanidines and furoxans; evaluating the antiasthmatic effects of coupled compounds by determining their inhibitory activity of guinea pig asthma induced by acetylcholine and histamine; and assessing NO releasing ability.

RESULTSNine novel target compounds (I1-9) were synthesized, and their structures were established by IR, NMR, MS and elemental analysis. Preliminary pharmacological test showed that most of the compounds showed high antiasthmatic activities (the latent period of induced asthma was prolonged from 10 s (SD) to 26-62 s), among which 3 compounds (I4, I6, I7) were more potent than SD (P < 0.05, P < 0.01) and released more NO than others. The maximum concentrations (Cmax) of NO-release in vitro were 0.1878, 0.1393 and 0.2473 mg x L(-1), respectively.

CONCLUSIONNO donating-SD derivatives are worthy to be futher investigated.

Acetylcholine ; Animals ; Anti-Asthmatic Agents ; chemical synthesis ; pharmacology ; therapeutic use ; Asthma ; chemically induced ; prevention & control ; Benzoquinones ; chemical synthesis ; pharmacology ; therapeutic use ; Guanidines ; chemistry ; pharmacology ; Guinea Pigs ; Heptanoic Acids ; chemical synthesis ; pharmacology ; therapeutic use ; Histamine ; Nitric Oxide ; metabolism ; Nitric Oxide Donors ; chemistry ; pharmacology ; Oxadiazoles ; chemistry ; pharmacology ; Structure-Activity Relationship

BACKGROUNDThe aim of this study was to investigate the possible effect of somatostatin on the liver function of recipients undergoing living donor liver transplantation.

METHODSForty recipients were randomized into group A (n = 20) and group B (n = 20). Recipients in group A received no somatostatin whereas somatostatin was administrated for recipients in group B perioperatively. Liver function, the plasma concentration of endothelin-1 and nitric oxide, the intragraft expressions of endothelin-1 and inducible nitric oxide syntheses at 2 hours after declamping of the portal vein were compared between the two groups.

RESULTSCompared to group A, alanine transaminase values in group B were significantly reduced at 2 hours after portal vein declamping, at the end of the operation and postoperation day 1 (P < 0.05), whereas aspartate aminotransferase values in group B decreased at 30 minutes after portal vein clamping, at 2 hours after portal vein declamping and at the end of the operation (P < 0.05). Total bilirubin values in group B were reduced significantly at 2 hours after portal vein declamping and at the end of the operation when compared to group A (P < 0.05). Intragraft expression of endothelin-1 was significantly downregulated at 2 hours after declamping of the portal vein accompanied with a reduction of plasma concentration of endothelin-1 in the peripheral blood (P < 0.05).

CONCLUSIONSSomatostatin had a protective effect on liver function during the early phase after declamping of portal vein for recipients undergoing living donor liver transplantation, and the possible mechanism might be partially attributed to the downregulation of endothelin-1.

Adult ; Down-Regulation ; drug effects ; Endothelin-1 ; blood ; Female ; Hormones ; pharmacology ; therapeutic use ; Humans ; Immunohistochemistry ; Liver ; drug effects ; Liver Transplantation ; methods ; Living Donors ; Male ; Middle Aged ; Nitric Oxide ; blood ; Somatostatin ; pharmacology ; therapeutic use

OBJECTIVETo compare the therapeutic effect of recombinant human brain natriuretic peptide (rhBNP) and nitroglycerin on acute decompensated heart failure (ADHF).

METHODSFifty ADHF patients were randomly divided into rhBNP group and nitroglycerin group. In all the patients, dyspnea and global clinical status were assessed before and at 30 min, 6 h and 24 h after drug administration, and the volume of fluid intake and urine along with hemodynamic parameters was recorded 24 h after drug administration. In the nitroglycerin group, the patients received an initial nitroglycerin dose of 5 microg/min, with subsequent dose increment of 5 microg/min every 3 to 5 min; the dose was adjusted individually according to the hemodynamics of the patients. The patients in rhBNP group were given rhBNP at the initial dose of 1.5 microg/kg by with an intravenous bolus injection followed by infusion at the rate of 0.0075 microg.kg(-1).min(-1) for 72 h.

RESULTSAt 30 min and 6 h after drug administration, the patients in the rhBNP group showed significant greater improvement of dyspnea (P=0.042 and 0.019) and global clinical status (P=0.018 and 0.044) than those in the nitroglycerin group, but 24 h after drug administration, no significant difference was noted between the two groups (P=0.192 and 0.179). Twenty-four hours after drug administration, the mean urine volume was significantly greater in rhBNP group than in nitroglycerin group (1513.8-/+242.9 vs 1341.2-/+239.7 ml, P=0.015), and the ejection fraction increased and pulmonary arterial pressure and systolic blood pressure decreased at greater amplitude in the former group (P=0.001,0.000 and 0.002, respectively). At 72 h, the numbers of premature ventricular contraction and couplets premature beats and onset of paroxysmal ventricular tachycardia were significantly reduced in rhBNP group as compared with the nitroglycerin group (P=0, 0.001 and 0.002, respectively).

CONCLUSIONRhBNP promotes urine excretion, decreases pulmonary arterial pressure and increases left ventricular ejection fraction to improve dyspnea and global clinical status and reduce the onset of ventricular arrhythmia in ADHF patients.

Aged ; Aged, 80 and over ; Blood Pressure ; drug effects ; Female ; Heart Failure ; drug therapy ; pathology ; physiopathology ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; administration & dosage ; genetics ; therapeutic use ; Nitric Oxide Donors ; administration & dosage ; therapeutic use ; Nitroglycerin ; administration & dosage ; therapeutic use ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Treatment Outcome

AIMTo search for new derivatives of diclofenac (DC) having higher potency than the parent drug and lacking its undesirable effects.

METHODSCoupling DC with NO donor 3-hydroxymethyl-4-phenylfuroxan and its isomer through esterification, evaluating anti-inflammatory and analgesic activities, observing side effects in the rat gastrointestinal (GI) tract and assessing NO releasing ability both in vitro and in vivo.

RESULTSFifteen new compounds including nine target ones (II1-9) were synthesized, and their structures were determined by IR, 1HNMR, MS and elemental analysis. Compounds II3 and II9 showed anti-inflammatory activity comparable to DC. Compound II2 showed stronger anti-inflammatory and analgesic activities and less GI side effect than DC, and released NO in vivo.

CONCLUSIONCompound II2 is worthy to be intensively studied.

Analgesics ; chemical synthesis ; pharmacology ; therapeutic use ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; chemical synthesis ; pharmacology ; therapeutic use ; Cyclic N-Oxides ; administration & dosage ; chemistry ; pharmacology ; Diclofenac ; chemical synthesis ; pharmacology ; therapeutic use ; Digestive System ; drug effects ; Edema ; drug therapy ; Gastrointestinal Hemorrhage ; chemically induced ; Mice ; Molecular Structure ; Nitric Oxide ; metabolism ; Nitric Oxide Donors ; chemistry ; pharmacology ; Oxadiazoles ; administration & dosage ; chemistry ; pharmacology ; Pain Threshold ; drug effects ; Rats ; Structure-Activity Relationship