BACKGROUNDNitroglycerin (NTG) is one of the few immediate treatments for acute angina. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in the human body that facilitates the biological metabolism of NTG. The biological mechanism of NTG serves an important function in NTG efficacy. Some reports still contradict the results that the correlation between ALDH2 gene polymorphisms and NTG and its clinical efficacy is different. However, data on NTG measurement by pain relief are subjective. This study aimed to investigate the influence of ALDH2 gene polymorphism on intervention with sublingual NTG using noninvasive hemodynamic parameters of cardiac output (CO) and systemic vascular resistance (SVR) in Northern Chinese Han population.

METHODSThis study selected 559 patients from the Affiliated Hospital of Qingdao University. A total of 203 patients presented with coronary heart disease (CHD) and 356 had non-CHD (NCHD) cases. All patient ALDH2 genotypes (G504A) were detected and divided into two types: Wild (GG) and mutant (GA/AA). Among the CHD group, 103 were wild-type cases, and 100 were mutant-type cases. Moreover, 196 cases were wild-type, and 160 cases were mutant type among the NCHD volunteers. A noninvasive hemodynamic detector was used to monitor the CO and the SVR at the 0, 5, and 15 minute time points after medication with 0.5 mg sublingual NTG. Two CO and SVR indicators were used for a comparative analysis of all case genotypes.

RESULTSBoth CO and SVR indicators significantly differed between the wild and mutant genotypes at various time points after intervention with sublingual NTG at 5 and 15 minutes in the NCHD (F = 16.460, 15.003, P = 0.000, 0.000) and CHD groups (F = 194.482, 60.582, P = 0.000, 0.000). All CO values in the wild-type case of both NCHD and CHD groups increased, whereas those in the mutant type decreased. The CO and ΔCO differences were statistically significant (P < 0.05; P < 0.05). The SVR and ΔSVR changed between the wild- and mutant-type cases at all-time points in both NCHD and CHD groups had statistically significant differences (P < 0.05; P < 0.05).

CONCLUSIONALDH2 (G504A) gene polymorphism is associated with changes in noninvasive hemodynamic parameters (i.e. CO and SVR) after intervention with sublingual NTG. This gene polymorphism may influence the effect of NTG intervention on Northern Chinese Han population.

Aged ; Aldehyde Dehydrogenase ; genetics ; Aldehyde Dehydrogenase, Mitochondrial ; Asian Continental Ancestry Group ; Female ; Hemodynamics ; drug effects ; genetics ; physiology ; Humans ; Male ; Middle Aged ; Nitroglycerin ; pharmacology ; Polymorphism, Genetic ; genetics

The present study aimed at evaluation of prophylactic efficacy and possible mechanisms of asiaticoside (AS) based standardized extract of Centella asiatica (L.) Urban leaves (INDCA) in animal models of migraine. The effects of oral and intranasal (i.n.) pretreatment of INDCA (acute and 7-days subacute) were evaluated against nitroglycerine (NTG, 10 mg·kg(-1), i.p.) and bradykinin (BK, 10 μg, intra-arterial) induced hyperalgesia in rats. Tail flick latencies (from 0 to 240 min) post-NTG treatment and the number of vocalizations post-BK treatment were recorded as a measure of hyperalgesia. Separate groups of rats for negative (Normal) and positive (sumatriptan, 42 mg·kg(-1), s.c.) controls were included. The interaction of INDCA with selective 5-HT1A, 5-HT1B, and 5-HT1D receptor antagonists (NAN-190, Isamoltane hemifumarate, and BRL-15572 respectively) against NTG-induced hyperalgesia was also evaluated. Acute and sub-acute pre-treatment of INDCA [10 and 30 mg·kg(-1) (oral) and 100 μg/rat (i.n.) showed significant anti-nociception activity, and reversal of the NTG-induced hyperalgesia and brain 5-HT concentration decline. Oral pre-treatment with INDCA (30 mg·kg(-1), 7 d) showed significant reduction in the number of vocalization. The anti-nociceptive effects of INDCA were blocked by 5-HT1A and 5-HT1B but not 5-HT1D receptor antagonists. In conclusion, INDCA demonstrated promising anti-nociceptive effects in animal models of migraine, probably through 5-HT1A/1B medicated action.
Administration, Intranasal ; Administration, Oral ; Animals ; Bradykinin ; Female ; Hyperalgesia ; chemically induced ; prevention & control ; Male ; Migraine Disorders ; chemically induced ; prevention & control ; Models, Animal ; Nitroglycerin ; Nociception ; drug effects ; Plant Leaves ; chemistry ; Pre-Exposure Prophylaxis ; Rats ; Rats, Wistar ; Reaction Time ; Receptors, Serotonin, 5-HT1 ; drug effects ; Serotonin 5-HT1 Receptor Antagonists ; metabolism ; Tail ; physiology ; Triterpenes ; administration & dosage ; pharmacology

OBJECTIVE: To investigate the protective effect of combined administration of verapamil and nitroglycerin on the function of canine transplanted lungs. METHODS: Twenty orthotopic left lung transplantations were performed in 40 canines, which were randomly divided into 4 groups. In group I (control), the donor lungs were perfused and preserved with LPD solution, while group II with LPD solution plus verapamil 0.1 g/L, group III with LPD solution plus nitroglycerin 0.1g/L, and group IV with LPD solution plus verapamil 0.1 g/L and nitroglycerin 0.1 g/L. Hemodynamics and graft gas exchange were assessed 0, 2 and 4 h after the operation. The lung grafts were harvested to measure the wet/dry weight ratio, malondialdehyde (MDA) contents and superoxide dismutase (SOD) activity. RESULTS: Compared with group I, II and III, the mean pulmonary artery pressure (MPAP), pulmonary vascular resistance index (PVRI), partial pressure of oxygen in arterial blood (PaO₂), dynamic compliance (Cdyn) and alveolar-arterial oxygen tension volume [P(A- a)O₂] in group IV were improved significantly (P<0.05). No significant difference in the partial pressure of carbondioxide (PaCO₂) and peak inspiratory pressure (PIP) was observed in the 4 groups (P>0.05). In group IV, the wet/dry weight ratio and MDA contents were lower than those in the other 3 groups, and the SOD activity was significantly higher than that of the other 3 groups (P<0.05). CONCLUSION Verapamil and nitroglycerin in LPD solution can protect the respiratory function of canine lung grafts by attenuating pulmonary edema and oxidative stress.
Animals ; Blood Gas Analysis ; Dogs ; Hemodynamics ; Lung ; Lung Transplantation ; Nitroglycerin ; pharmacology ; Organ Preservation ; Protective Agents ; Reperfusion Injury ; Verapamil ; pharmacology

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs 5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3 vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).
Adiponectin/blood ; Aged ; Aged, 80 and over ; Atherosclerosis/complications/drug therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nitroglycerin/therapeutic use ; Prospective Studies ; Pyrazines/pharmacology/*therapeutic use ; Regression Analysis ; Triazoles/pharmacology/*therapeutic use ; Vasodilation/drug effects ; Vasodilator Agents/therapeutic use

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs 5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3 vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).
Adiponectin/blood ; Aged ; Aged, 80 and over ; Atherosclerosis/complications/drug therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nitroglycerin/therapeutic use ; Prospective Studies ; Pyrazines/pharmacology/*therapeutic use ; Regression Analysis ; Triazoles/pharmacology/*therapeutic use ; Vasodilation/drug effects ; Vasodilator Agents/therapeutic use

OBJECTIVETo study the clinical value and safety of the head-up tilt table test (HUTT) in children under 6 years old.

METHODSThe HUTT results between September 2000 and August 2011 of 144 2 to 6-year-old children (81 boys and 63 girls) with syncope and dizziness of unknown causes were retrospectively studied.

RESULTSEight children completed the based tilt table test and 136 cases completed the sublingual nitroglycerin tilt table test. No serious side effects were found in these children. Thirty-two (22.2%) of the 144 children had a positive result of HUTT, including 18 boys and 14 girls (P>0.05). When HUTT-induced syncope met positive standards, ECG record and blood pressure recovered to normal levels within 5 minutes by changing the position of the test bed, keeping the airway open, nasal oxygen inhalation and oral milk.

CONCLUSIONSThe HUTT is valuable, safe and compliant in children under 6 years old.

Age Factors ; Blood Pressure ; drug effects ; Child ; Child, Preschool ; Dizziness ; diagnosis ; physiopathology ; Electrocardiography ; drug effects ; Female ; Humans ; Male ; Nitroglycerin ; pharmacology ; Retrospective Studies ; Syncope ; diagnosis ; physiopathology ; Tilt-Table Test

OBJECTIVETo evaluate the effect of tetrandrine (Tet) on nitroglycerin(GTN)-induced activation of the satellite cells released inflammatory cytokines and to explore its mechanism.

METHODNeonatal rat satellite cells of trigeminal ganglia were cultured and separated into three groups. Group CON: the cells were normal cultured; Group TGN: the cells were cultured with 0.55 mmol x L(-1) GTN; Group Tet: the cells were treated with 0.55 mmol x L(-1) GTN and 1 x 10(-7) mol x L(-1) Tet respectively. Cell viability after GTN and Tet was detected by AlamarBlue assay. The concentration change of intracellular Ca2+ ([Ca2+]i) in single satellite cell loaded with Fluo-3/AM was determined by laser scanning confocal microscopy. NF-kappaB and IL-1beta mRNA levels were determined by FQ-PCR. Through double-immunofluorescent staining identifies satellite cells and determines the expression of NF-kappaB protein.

RESULTSatellite cells activities decreased with GTN stimulating, but according to the viability and modality of the cells, 1 x 10(-7) mol x L(-1) Tet was the suitable prophylaxis. Tet can inhibit the elevation of cytosolic free calcium of rat satellite cell and decrease the mRNA and protein levels of NF-kappaB and the mRNA levels of IL-1beta.

CONCLUSIONVia preventing Ca2+ influxion, Tet inhibited NF-kappaB activation of satellite cell which decreased IL-1beta expression.

Animals ; Benzylisoquinolines ; pharmacology ; Calcium ; metabolism ; Calcium Channel Blockers ; pharmacology ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation ; drug effects ; Interleukin-1beta ; genetics ; NF-kappa B ; genetics ; metabolism ; Nitroglycerin ; pharmacology ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Satellite Cells, Perineuronal ; drug effects ; metabolism ; Trigeminal Ganglion ; drug effects ; metabolism

OBJECTIVETo compare the relief effect of diltiazem, papaverine and nitroglycerin on radial artery spasm in elderly patients with coronary atherosclerotic heart disease.

METHODSSixty patients aged beyond 70 years underwent coronary artery bypass grafting (CABG) with autologous radial artery from July 2009 to March 2010. Redundant radial artery was collected and the relief function of different drugs was evaluated through "organ bath" technique in vitro. All the patients were randomly divided into 3 groups based on different antispasmodic drugs: diltiazem, papaverine and nitroglycerin. Thirty seconds free blood flow of radial artery and hemodynamic parameters (heart rate, mean arterial pressure and central venous pressure) were assessed before and after intra-radial administration of diltiazem, papaverine and nitroglycerin in vivo.

RESULTSAll three drugs could relieve radial artery spasm in different levels and the eventual relief rate was over 80%. Only nitroglycerin could relax radial artery completely, the relief capacity of nitroglycerin, diltiazem and papaverine decreased in order. There was no significant difference in the hemodynamic parameters before and after the injection. Blood flow of radial artery increased in nitroglycerin group [(42 ± 10) ml/30 s vs. (28 ± 7) ml/30 s, P < 0.05] while there was no significant difference in diltiazem [(23 ± 10) ml/30 s vs. (25 ± 8) ml/30 s, P > 0.05] and papaverine group [(25 ± 10) ml/30 s vs. (24 ± 9), P > 0.05].

CONCLUSIONSNitroglycerin could relieve vasospasm of radial artery effectively and increased blood flow. Nitroglycerin is the suitable antispasmodic drug for radial artery in the elderly patients with coronary atherosclerotic heart disease compare with diltiazem and papaverine.

Aged ; Aged, 80 and over ; Coronary Artery Bypass ; Coronary Artery Disease ; physiopathology ; surgery ; Diltiazem ; pharmacology ; Female ; Follow-Up Studies ; Humans ; Male ; Nitroglycerin ; pharmacology ; Papaverine ; pharmacology ; Parasympatholytics ; pharmacology ; Radial Artery ; drug effects ; physiology ; transplantation

This study investigated whether trinitroglycerine (TNG) as nitric oxide (NO) releasing agent had anti-leishmanial effects and mediated pathology in BALB/c mice infected with Leishmania major. Cutaneous leishmaniasis (CL), a zoonotic infection caused by leishmania protozoa is still one of the health problems in the world and in Iran. NO is involved in host immune responses against intracellular L. major, and leishmania killing by macrophages is mediated by this substance. Moreover, application of CL treatment with NO-donors has been recently indicated. In our study, TNG was used for its ability to increase NO and to modify CL infection in mice, in order to evaluate NO effects on lesion size and formation, parasite proliferation inside macrophages, amastigote visceralization in target organs, and NO induction in plasma and organ suspensions. Data obtained in this study indicated that TNG increased plasma and liver-NO, reduced lesion sizes, removed amastigotes from lesions, livers, spleens, and lymph nodes, declined proliferation of amastigotes, hepatomegaly, and increased survival rate. However, TNG reduced spleen-NO and had no significant effects on spelenomegaly. The results show that TNG therapy reduced leishmaniasis and pathology in association with raised NO levels. TNG had some antiparasitic activity by reduction of positive smears from lesions, livers, spleens, and lymph nodes, which could emphasize the role of TNG to inhibit visceralization of L. major in target organs.
Animal Structures/parasitology ; Animals ; Antiprotozoal Agents/chemistry/*therapeutic use ; Female ; Leishmania major/*drug effects/immunology ; Leishmaniasis, Cutaneous ; Macrophages/parasitology ; Mice ; Mice, Inbred BALB C ; Nitric Oxide/blood/metabolism/*pharmacology ; Nitroglycerin/*analogs & derivatives/*therapeutic use ; Severity of Illness Index ; Skin/pathology ; Survival Analysis

OBJECTIVETo investigate the effects of nitroglycerine (NTG) on myocardial oxygen metabolism and regional cardiac function in canine hearts with a stable systemic hemodynamics in situ.

METHODSEight anesthetized open-chest dogs with flow-limited left anterior descending branch of the coronary artery or left circumflex artery (LCx) stenosis were studied. The percentage of ventricular wall thickening (%WT) was measured with quantitative two-dimensional echocardiography (2DE), myocardial blood flow (MBF) with radiolabeled microspheres and tissue oxygen pressure (tPO(2).) with oxygen-dependent quenching of phosphorescence. 2DE was performed and radiolabeled microspheres and Pd-porphyrin injected in the dogs at rest during intracoronary infusion of 0.3-0.6 mg x kg(-1) x min(-1) of NTG. Myocardial oxygen consumption (MVO(2), ml x min(-1) x 100 g(-1)) was calculated as the multiplication product between the arterio-venous oxygen content difference and MBF, and myocardial O(2) delivery as the product between arterial oxygen content and MBF.

RESULTSAs compared with the baseline, NTG increased %WT and MBF significantly in both normal and ischemic beds (P<0.05). There was a significant increase in MVO(2) during NTG infusion in the ischemic bed (P<0.05) in comparison with that measured at rest. NTG, however, significantly increased the ability of myocardial O(2) delivery in both normal and ischemic beds (P<0.05), therefore tPO(2) was still higher in the ischemic bed during NTG infusion than that at rest (P<0.05). The percentage increment in tPO(2) was significantly greater in the ischemic bed than percentage MBF increment.

CONCLUSIONSNTG enhances myocardial oxygen concentration in normal and ischemic myocardium and may increase oxygen release to the ischemic myocardium in vivo. NTG may have a positive inotropic effect on regional cardiac function. In addition to direct effect on vascular tone, NTG plays important roles in the cardiovascular system by modulating myocardial oxygen metabolism and contractile function.

Animals ; Dogs ; Echocardiography ; Hemodynamics ; Myocardium ; metabolism ; Nitroglycerin ; pharmacology ; Oxygen Consumption ; drug effects