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‣ Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway

Mao, Mao; Sudhahar, Varadarajan; Ansenberger-Fricano, Kristine; Fernandes, Denise C.; Tanaka, Leonardo Y.; Fukai, Tohru; Laurindo, Francisco R. M.; Mason, Ronald P.; Vasquez-Vivar, Jeannette; Minshall, Richard D.; Stadler, Krisztian; Bonini, Marcelo G.
Fonte: ELSEVIER SCIENCE INC; NEW YORK Publicador: ELSEVIER SCIENCE INC; NEW YORK
Tipo: Artigo de Revista Científica
Português
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Nitroglycerin (GIN) has been clinically used to treat angina pectoris and acute heart episodes for over 100 years. The effects of GTN have long been recognized and active research has contributed to the unraveling of numerous metabolic routes capable of converting GIN to the potent vasoactive messenger nitric oxide. Recently, the mechanism by which minute doses of GIN elicit robust pharmacological responses was revisited and eNOS activation was implicated as an important route mediating vasodilation induced by low GTN doses (1-50 nM). Here, we demonstrate that at such concentrations the pharmacologic effects of nitroglycerin are largely dependent on the phosphatidylinositol 3-kinase, Akt/PKB, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signal transduction axis. Furthermore, we demonstrate that nitroglycerin-dependent accumulation of 3,4,5-InsP(3), probably because of inhibition of PTEN, is important for eNOS activation, conferring a mechanistic basis for GIN pharmacological action at pharmacologically relevant doses. (C) 2011 Elsevier Inc. All rights reserved.; National Institute of Environmental Health Sciences Division of Intramural Research, an American Heart Association [09SDG2250933]; National Institute of Environmental Health Sciences Division of Intramural Research...

‣ The effects of local nitroglycerin on the surgical delay procedure in prefabricated flaps by vascular implant in rats

Sá,Jairo Zacchê de; Aguiar,José Lamartine de Andrade; Cruz,Adriana Ferreira; Schuler,Alexandre Ricardo Pereira; Lima,José Ricardo Alves de; Marques,Olga Martins
Fonte: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia Publicador: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2012 Português
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PURPOSE: To evaluate the effect of local nitroglycerin on the viable area of a prefabricated flap for vascular implant in rats, and to investigate the surgical delay procedure. METHODS: A femoral pedicle was implanted under the skin of the abdominal wall in forty Wistar rats. The animals were divided into four groups of ten: group 1 - without surgical delay procedure and local nitroglycerin; group 2 - with surgical delay procedure, but without local nitroglycerin; group 3 - without surgical delay procedure, but with local nitroglycerin; and group 4 - with simultaneous surgical delay procedure and local nitroglycerin. The percentages of the viable areas, in relation to the total flap, were calculated using AutoCAD R 14. RESULTS: The mean percentage value of the viable area was 8.9% in the group 1. 49.4% in the group 2; 8.4% in the group 3 and 1.1% in the group 4. There was significant difference between groups 1 and 2 (p=0.005), 1 and 4 (p=0.024), 2 and 3 (p=0.003), 2 and 4 (p=0.001). These results support the hypothesis that the closure of the arterial venous channels is responsible for the phenomenon of surgical delay procedure. CONCLUSION: Local nitroglycerin did not cause an increase in the prefabricated viable flap area by vascular implantation and decreased the viable flap area that underwent delay procedures.

‣ Nitroglycerin and Heterogeneity of Myocardial Blood Flow REDUCED SUBENDOCARDIAL BLOOD FLOW AND VENTRICULAR CONTRACTILE FORCE

Forman, Robert; Kirk, Edward S.; Downey, James M.; Sonnenblick, Edmund H.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1973 Português
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The effects of both intracoronary and intravenous administration of nitroglycerin on transmural distribution of blood flow in the left ventricle after partial coronary artery occlusion was investigated using two independent methods. In 16 open chest, anesthetized dogs, tubing supplying the cannulated left coronary artery was partially occluded. Strain gauges sutured paralled to superficial and deep fibers of the myocardium separately recorded the contractile force of each layer. With occlusion set so that depression of the deep contractile force was imminent. 12 μg intracoronary nitroglycerin in seven dogs depressed only the deep contractile force without changing systemic hemodynamics. Intravenous administration of 180 μg nitroglycerin in nine dogs resulted in a decrease of deep contractile force and aortic pressure often associated with an increase in superficial contractile force. Distribution of myocardial blood flow during peak coronary flow after intracoronary administration of nitroglycerin or during a decrease in aortic pressure after intravenous nitroglycerin administration was determined by the tissue uptake of an intracoronary bolus of rubidium-80. This was compared with the uptake of potassium-42 injected before nitroglycerin. Intravenous or intracoronary administration of nitroglycerin caused a significant reduction in subendocardial blood flow with a decrease in the subendocardial/subepicardial ratio of isotope.

‣ Comparison of Nitroglycerin-, Nitroprusside-, and Phentolamine-Induced Changes in Coronary Collateral Function in Dogs

Capurro, Norine L.; Kent, Kenneth M.; Epstein, Stephen E.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1977 Português
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The recent use of vasodilators to improve ventricular function in acute myocardial infarction led us to investigate the effects of nitroglycerin, nitroprusside, and phentolamine on coronary collateral flow. Dogs were studied 2-4 wk after an ameroid constrictor was placed around the left anterior descending (LAD) coronary artery. Retrograde flow and peripheral coronary pressure were measured from a cannula inserted in the LAD distal to the ameroid. Systemic arterial pressure was held constant by an aortic cuff. When administered intracoronary (i.c.), nitroglycerin, 0.3-100 μg/min, or nitroprusside, 3-100 μg/min, produced quantitatively similar, dose-dependent increases in retrograde flow. Neither drug, i.c., changed peripheral coronary pressure. Nitroglycerin, 3-300 μg/min, intravenous (i.v.), produced dose-dependent increases in retrograde flow; nitroprusside, i.v., increased retrograde flow only in high doses (100-300 μg/min). Nitroglycerin and nitroprusside, i.v., produced similar increases in peripheral coronary pressure. Phentolamine, 1-300 μg/min, i.v., decreased retrograde flow, and did not change peripheral coronary pressure. Nitroprusside was considerably more potent than nitroglycerin in decreasing systemic arterial pressure and in reducing total coronary resistance. Thus...

‣ Nitroglycerin and premature ventricular complexes in myocardial infarction.

Knoebel, S B; Rasmussen, S; Noble, R J; Mihalick, M J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1975 Português
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Because of clinical observations suggesting that nitroglycerin may suppress premature ventricular complexes during acute ischaemia, a study was undertaken to assess the effect of nitroglycerin on the incidence of premature ventricular complexes in patients with acute myocardial infarction. Forty patients with acute myocardial infarction were studied. Twenty-six patients received 0.4 mg nitroglycerin sublingually every 4 hours for the first 24 hours after admission to the coronary care unit. The total premature ventricular complex count for the 26 patients for 15 minutes before nitroglycerin was 592, and 276 for the 15 minutes after the drug (P less than 0.005). In the remaining 14 patients on the same nitroglycerin schedule, a single electrocardiographic lead was continuously recorded on tape. During the first hour after nitroglycerin, the premature ventricular complex count decreased by 58 per cent, and the second and third hours showed a decrease from control count of 71 and 65 per cent respectively. By the end of 4 hours the ectopic count was back to control level. The data indicate that nitroglycerin may decrease the number of premature ventricular complexes for up to 3 hours in patients with acute myocardial infarction. The mechanism of action of nitroglycerin is not elucidated by this study...

‣ Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase. A new action for an old drug.

Münzel, T; Kurz, S; Rajagopalan, S; Thoenes, M; Berrington, W R; Thompson, J A; Freeman, B A; Harrison, D G
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/09/1996 Português
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Hydralazine has been shown to reduce mortality in patients with congestive heart failure when given concomitantly with isosorbide dinitrate. Recently, we demonstrated that nitrate tolerance is in part due to enhanced vascular superoxide .O2- production. We sought to determine mechanisms whereby hydralazine may prevent tolerance. Rabbits either received no treatment, nitroglycerin patches (1.5 micrograms/kg/min x 3 d), hydralazine alone (10 mg/kg/d in drinking water), or hydralazine and nitroglycerin. Aortic segments were studied in organ chambers and relative rates of vascular .O2- production were determined using lucigenin-enhanced chemiluminescence. Nitroglycerin treatment markedly inhibited relaxations to nitroglycerin (maximum relaxations in untreated: 92 +/- 1 vs. 64 +/- 3% in nitroglycerin-treated patients and increased vascular .O2- production by over two-fold (P < 0.05). Treatment with hydralazine in rabbits not receiving nitroglycerin significantly decreased .O2- production in intact rabbit aorta and increased sensitivity to nitroglycerin. When given concomitantly with nitroglycerin, hydralazine completely prevented the development of nitrate tolerance and normalized endogenous rates of vascular .O2- production. Studies of vessel homogenates demonstrated that the major source of .O2- was an NADH-dependent membrane-associated oxidase displaying activities of 67 +/- 12 vs. 28 +/- 2 nmol .O2-.min-1.mg protein-1 in nitroglycerin-treated vs. untreated aortic homogenates. In additional studies...

‣ Nitroglycerin metabolism in vascular tissue: role of glutathione S-transferases and relationship between NO. and NO2- formation.

Kurz, M A; Boyer, T D; Whalen, R; Peterson, T E; Harrison, D G
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/06/1993 Português
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Nitroglycerin is a commonly employed pharmacological agent which produces vasodilatation by release of nitric oxide (NO.). The mechanism by which nitroglycerin releases NO. remains undefined. Recently, glutathione S-transferases have been implicated as important contributors to this process. They are known to release NO2- from nitroglycerin, but have not been shown to release NO.. The present studies were designed to examine the role of endogenous glutathione S-transferases in this metabolic process. Homogenates of dog carotid artery were incubated anaerobically with nitroglycerin, and NO. and NO2- production was determined by chemiluminescence. The role of glutathione S-transferases was studied by incubating homogenates with nitroglycerin in the presence of 1 mM GSH or 1 mM S-hexyl-glutathione, a potent inhibitor of glutathione S-transferases. Homogenates released 163 pmol of NO./h per mg of protein from nitroglycerin, and 2370 pmol of NO2-/h per mg. Adding GSH decreased NO. production by 82% and increased NO2- production by 98%. S-Hexylglutathione inhibited glutathione S-transferase activity by 96% and decreased NO2- production by 78%, but had no effect on NO. release. A linear relationship between glutathione S-transferase activity and NO2- production was observed...

‣ Plasma levels of nitroglycerin generated by three nitroglycerin patch preparations, Nitradisc, Transiderm-Nitro and Nitro-Dur and one ointment formulation, Nitrobid.

McAllister, A; Mosberg, H; Settlage, J A; Steiner, J A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1986 Português
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Twenty-four healthy male subjects participated in a study comparing plasma concentrations of nitroglycerin generated by single applications of Nitradisc 32 mg, Transiderm-Nitro 50 mg and Nitro-Dur 104 mg patches and from one inch of Nitrobid 2% ointment. The three patch preparations are designed to release 10 mg nitroglycerin systemically over a 24 h period. Nitrobid ointment is intended to deliver 15 mg nitroglycerin per inch of ointment, and to be reapplied at least every 8 h. Blood was taken for nitroglycerin assay up to and including 24 h after each application. Assay for nitroglycerin was performed using a gas chromatography-mass spectrometry technique. Plasma concentrations of nitroglycerin were sustained up to the 24 h mark with all three patch preparations, but not with application of Nitrobid ointment. Nitrobid was associated with a rapid rise in nitroglycerin plasma concentrations maximal 1 h after application. Plasma concentrations of nitroglycerin absorbed from Nitrobid ointment fell below those absorbed from all three patch preparations after 8 h. Clinically, all four formulations were similar with respect to side effects, with headache and dizziness being the most common.

‣ Nitroglycerin Use in Myocardial Infarction Patients: Risks and Benefits

Ferreira, Julio C.B.; Mochly-Rosen, Daria
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Acute myocardial infarction and its sequelae are leading causes of morbidity and mortality worldwide. Nitroglycerin remains a first-line treatment for angina pectoris and acute myocardial infarction. Nitroglycerin achieves its benefit by giving rise to nitric oxide, which causes vasodilation and increases blood flow to the myocardium. However, continuous delivery of nitroglycerin results in tolerance, limiting the use of this drug. Nitroglycerin tolerance is due, at least in part, to inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme that converts nitroglycerin to the vasodilator, nitric oxide. We have recently found that, in addition to nitroglycerin’s effect on the vasculature, sustained treatment with nitroglycerin negatively affects cardiomyocyte viability following ischemia, thus resulting in increased infarct size in a myocardial infarction model in animals. Co-administration of Alda-1, an activator of ALDH2, with nitroglycerin improves metabolism of reactive aldehyde adducts and prevents the nitroglycerin-induced increase in cardiac dysfunction following myocardial infarction. In this review, we describe the molecular mechanisms associated with the benefits and risks of nitroglycerin administration in myocardial infarction. (167 of 200).

‣ ALDH2 Activator Inhibits Increased Myocardial Infarction Injury by Nitroglycerin Tolerance

Sun, Lihan; Ferreira, Julio Cesar Batista; Mochly-Rosen, Daria
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 02/11/2011 Português
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Nitroglycerin, which helps impaired cardiac function as it is converted to nitric oxide, is used worldwide to treat patients with various ischemic and congestive cardiac diseases, including angina pectoris. Nevertheless, after continuous treatment, the benefits of nitroglycerin are limited by the development of tolerance to the drug. Nitroglycerin tolerance is a result of inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme essential for cardioprotection in animals subjected to myocardial infarction (MI). Here we tested the hypothesis that the tolerance that develops as a result of sustained nitroglycerin treatment increases cardiac injury by subsequent MI. In a rat model of MI, 16 hours of prior, sustained nitroglycerin treatment (7.2 mg/kg/day) resulted in infarcts that were twice as large as those in untreated control animals and in diminished cardiac function at 3 days and 2 weeks after the MI. We also sought to identify a potential treatment to protect against this increased cardiac damage. Nitroglycerin inhibited ALDH2 activity in vitro, an effect that was blocked by Alda-1, an activator of ALDH2. Co-administration of Alda-1 (16 mg/kg/day) with the nitroglycerin prevented the nitroglycerin-induced increase in cardiac dysfunction after MI in rats...

‣ Nitroglycerin tolerance at the platelet level in patients with angina pectoris.

Chirkov, Y.; Chirkova, L.; Horowitz, J.
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Artigo de Revista Científica
Publicado em //1997 Português
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Suppression of platelet aggregation may be an important component of the therapeutic effect of nitroglycerin (NTG). Because of the phenomenon of hemodynamic tolerance to NTG, we tested the hypothesis that the anti-platelet effects of NTG in humans are also subject to tolerance induction. In patients with stable angina who had not received nitrates for at least 24 hours before study, sublingual administration of NTG (300 microg; n = 17) attenuated the reversal of adenosine diphosphate-induced platelet aggregation by NTG applied in vitro. Three minutes after in vivo NTG administration, concentration of NTG producing 50% reversal of aggregation (C50) increased from 7.9 +/- 1.9 x 10(-5) to 5.5 +/- 0.3 x 10(-4) M (p <0.01); this change persisted for at least 60 minutes. There was no concomitant change in C50 values for sodium nitroprusside applied in vitro. Basal activity of platelet guanylate cyclase and its response to sodium nitroprusside were not affected after administration of NTG. Brief intravenous infusion of NTG (10 microg/min for 10 minutes) produced no significant changes in platelet responses to NTG in vitro. However, prolonged infusion of NTG (5 microg/min for 24 hours, patients with unstable angina pectoris, n = 11) caused suppression of in vitro platelet response to NTG. Platelets from patients receiving prophylactic nitrates (n = 19) were less responsive to the antiaggregatory effects of NTG in vitro than those from patients who had not received nitrates in the previous 24 hours (n = 21). Thus...

‣ Effects of nitroglycerin on liquid gastric emptying and antropyloroduodenal motility

Sun, W.M.; Doran, S.; Jones, K.; Ooi, E.; Boeckxstaens, G.; Hebbard, G.; Lingenfelser, T.; Morley, J.; Dent, J.; Horowitz, M.
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
Publicado em //1998 Português
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The effects of the nitric oxide donor nitroglycerin on gastric emptying and antropyloroduodenal motility were evaluated in nine healthy male subjects (ages 19-36 yr). Antropyloroduodenal pressures were recorded with a manometric assembly that had nine side holes spanning the antrum and proximal duodenum and a pyloric sleeve sensor; gastric emptying was quantified scintigraphically. In each subject, the emptying of 300 ml of 25% glucose labeled with 99mTc was assessed on two separate days during intravenous infusion of either nitroglycerin (5 micrograms/min in 5% dextrose) or 5% dextrose (control). Studies were performed with the subject in the supine position; blood pressure and heart rate were monitored. Nitroglycerin had no significant effect on blood pressure or heart rate. Nitroglycerin slowed gastric emptying (P < 0.02), and this was associated with greater retention of the drink in the proximal stomach (P < 0.05). In both nitroglycerin and control studies, ingestion of the drink was associated with an increase in the number of isolated pyloric pressure waves (P < 0.05) and antral pressure wave sequences (P < 0.05). Nitroglycerin reduced the number of isolated pyloric pressure waves (P < 0.05), basal pyloric pressure (P < 0.05)...

‣ N-acetylcysteine potentiates nitroglycerin-induced reversal of platelet aggregation.

Chirkov, Y.; Horowitz, J.
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Artigo de Revista Científica
Publicado em //1996 Português
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N-Acetylcysteine (N-AC) potentiates the systemic and coronary hemodynamic and antianginal effects of nitroglycerin (NGT) in humans; NTG/N-AC reduces the incidence of acute myocardial infarction in patients with unstable angina pectoris. Although previous studies have demonstrated that NTG exerts antiaggregatory effects on platelets, little information is available concerning the possible potentiation by N-AC of NTG antiplatelet effects. In the present study, we examined the in vitro effects of NTG and the combination of NTG with N-AC on reversal of ADP-induced aggregation in platelet-rich plasma (PRP) obtained from normal subjects and patients with stable angina pectoris. We also examined the potential effect of background aspirin therapy on this interaction. NTG, added to platelets 0.5 min after the beginning of aggregation, suppressed the incipient aggregation and provoked the appearance of a disaggregation phase, resulting in a concentration-dependent reversal of platelet aggregation. Platelet responsiveness to NTG was significantly less (p < 0.01) in both groups of patients (receiving and not receiving aspirin) as compared with normal subjects. N-AC (10(-5) M), which did not in itself affect aggregation, induced a threefold potentiation (p < 0.05) of the antiaggregating effect of NTG that was similar in degree for all tested groups of individuals. This potentiation of the antiplatelet effects of NTG by N-AC may contribute to the efficacy of combined NTG/N-AC therapy in patients with acute ischemic syndromes.

‣ Nitroglycerin tolerance in human vessels: evidence for Impaired Nitroglycerin Bioconversion

Sage, P.; DeLaLande, I.; Stafford, I.; Bennett, C.; Phillipov, G.; Stubberfield, J.; Horowitz, J.
Fonte: Lippincott Williams & Wilkins Publicador: Lippincott Williams & Wilkins
Tipo: Artigo de Revista Científica
Publicado em //2000 Português
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Background—The basis for progressive attenuation of the effects of organic nitrates during long-term therapy (nitrate tolerance) remains controversial; proposed mechanisms include impaired nitrate bioconversion resulting in decreased release of nitric oxide (NO) from nitrates and/or increased NO clearance through a reaction with incrementally generated superoxide (O2–). Methods and Results—Patients undergoing elective coronary artery bypass were randomized to receive 24 hours of intravenously infused nitroglycerin (NTG; nitrate group) or no nitrate therapy (control group). Discarded segments of the internal mammary artery and saphenous vein were used to examine (1) vascular responsiveness to NTG, sodium nitroprusside, and the calcium ionophore A23187; (2) bioconversion of NTG to 1,2- and 1,3-glyceryl dinitrate; and (3) the generation of O2–. Responses to NTG were reduced 3- to 5-fold in vessels from the nitrate group compared with control vessels (P<0.01 for both types of segments), whereas responses to sodium nitroprusside and A23187 were unchanged. Tissue content of 1,2-glyceryl dinitrate was lower (P=0.012) in the saphenous veins from the nitrate group than in those from the control group. O2– generation was greater (P<0.01) in internal mammary artery samples from the nitrate group than in those from the control group. However...

‣ Effects of perhexiline and nitroglycerin on vascular, neutrophil and platelet function in patients with stable angina pectoris

Liberts, E.; Willoughby, S.; Kennedy, J.; Horowitz, J.
Fonte: Elsevier Science BV Publicador: Elsevier Science BV
Tipo: Artigo de Revista Científica
Publicado em //2007 Português
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Perhexiline, a "metabolic" anti-anginal agent currently under investigation in management of congestive heart failure and acute coronary syndromes improves platelet nitric oxide responsiveness in patients with impaired responsiveness. The current study investigated possible interactions between perhexiline and the nitric oxide donor nitroglycerin on arterial stiffness, neutrophil superoxide release and on platelet nitric oxide responsiveness. Patients (n=39) with stable angina pectoris, awaiting cardiac catheterization were randomized to additional perhexiline or unchanged drug therapy; all patients received nitroglycerin infusion for 2 h. Vasomotor responses to perhexiline and combined perhexiline/nitroglycerin were examined using changes in augmentation index, measured via applanation tonometry. Neutrophil superoxide release was measured ex vivo utilizing lucigenin mediated chemiluminescence and effect of perhexiline on inhibition of platelet aggregation by sodium nitroprusside was also measured. Perhexiline alone did not affect augmentation index, neutrophil superoxide release, or ex vivo platelet sodium nitroprusside response. Nitroglycerin decreased augmentation index (P<0.01) and superoxide release (P<0.05). Magnitude of inhibition of superoxide release was significantly enhanced by perhexiline pre-treatment (P<0.05); however perhexiline had no effect on magnitude of vasomotor response to nitroglycerin. In conclusion...

‣ Supplementation of University of Wisconsin solution with Nitroglycerin and Nicorandil in long-term myocardial preservation: effects on the oxidative state, endothelial function and morphology

Álvarez-Ayuso, Lourdes; García Gómez-Heras, Soledad; Jorge, Eduardo; Guardiola, José M.; Torralba, Amalia; Millán, Isabel; Roda, Jorge R.; Calero, Patricia; García-Poblete, Eduardo; Fernández-García, Héctor
Fonte: Murcia : F. Hernández Publicador: Murcia : F. Hernández
Tipo: Artigo de Revista Científica Formato: application/pdf
Português
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The purpose of this study was to assess the effects of the addition of Nitroglycerin or Nicorandil to University of Wisconsin solution in long-term myocardial preservation. In a model of heterotopic heart transplantation in pigs, the donor heart was preserved for 24 hours by means of continuous perfusion in this solution, in the presence or absence of these drugs. During this period, the oxygenation and pH of the solution were measured, as were lactate concentrations and enzyme release. At regular intervals following reperfusion we measured the concentrations of enzymes, antioxidants, glutathione peroxidase, glutathione reductase, malondialdehyde, endothelin and nitrite, and, two hours later, samples of both ventricles were taken for a morphological study. In the treated groups there was a higher lactate production during preservation and, during reperfusion, the signs of contracture and the elevation of enzyme levels were more marked than in the untreated groups. In contrast, the glutathione reductase concentrations did not decrease during the first phase of reperfusion and were directly correlated with those of antioxidants, endothelin levels increased less than in the untreated groups and, in the case of nitroglycerin, the nitrite concentration was significantly greater than in the remaining groups. We conclude that nitroglycerin and nicorandil improved the oxidative state and endothelial function and did not produce substantial morphological changes...

‣ Lidocaine alleviates propofol related pain much better than metoprolol and nitroglycerin

Goktug,Asutay; Gulec,Handan; Takmaz,Suna Akin; Turkyilmaz,Esra; Basar,Hulya
Fonte: Sociedade Brasileira de Anestesiologia Publicador: Sociedade Brasileira de Anestesiologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/10/2015 Português
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ABSTRACTBACKGROUND AND OBJECTIVES: Injection pain after propofol administration is common and maydisturb patients' comfort. The aim of this study was to compare effectiveness of intravenous(iv) nitroglycerin, lidocaine and metoprolol applied through the veins on the dorsum of hand orantecubital vein on eliminating propofol injection pain.METHOD: There were 147 patients and they were grouped according to the analgesic adminis-tered. Metoprolol (n = 31, Group M), lidocaine (n = 32, Group L) and nitroglycerin (n = 29, GroupN) were applied through iv catheter at dorsum hand vein or antecubital vein. Pain was evalu-ated by 4 point scale (0 - no pain, 1 --- light pain, 2 --- mild pain, 3 --- severe pain) in 5, 10, 15and 20th seconds. ASA, BMI, patient demographics, education level and the effect of pathwaysfor injection and location of operations were analyzed for their effect on total pain score.RESULTS: There were no differences between the groups in terms of total pain score (p = 0.981).There were no differences in terms of total pain score depending on ASA, education level,location of operation. However, lidocaine was more effective when compared with metoprolol(p = 0.015) and nitroglycerin (p = 0.001) among groups. Although neither lidocaine nor metopro-lol had any difference on pain management when applied from antecubital or dorsal hand vein(p > 0.05)...

‣ Repurposing Drugs in Oncology (ReDO)—nitroglycerin as an anti-cancer agent

Sukhatme, Vidula; Bouche, Gauthier; Meheus, Lydie; Sukhatme, Vikas P; Pantziarka, Pan
Fonte: Cancer Intelligence Publicador: Cancer Intelligence
Tipo: Artigo de Revista Científica
Português
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Nitroglycerin (NTG), a drug that has been in clinical use for more than a century, has a range of actions which make it of particular interest in an oncological setting. It is generally accepted that the main mechanism of action of NTG is via the production of nitric oxide (NO), which improves cardiac oxygenation via multiple mechanisms including improved blood flow (vasodilation), decreased platelet aggregation, increased erythrocyte O2 release and decreased mitochondrial utilization of oxygen. Its vasoactive properties mean that it has the potential to exploit more fully the enhanced permeability and retention effect in delivering anti-cancer drugs to tumour tissues. Moreover NTG can reduce HIF-1α levels in hypoxic tumour tissues and this may have anti-angiogenic, pro-apoptotic and anti-efflux effects. Additionally NTG may enhance anti-tumour immunity. Pre-clinical and clinical data on these anti-cancer properties of NTG are summarised and discussed. While there is evidence of a positive action as a monotherapy in prostate cancer, there are mixed results in NSCLC where initially positive results have yet to be fully replicated. Based on the evidence presented, a case is made that further exploration of the clinical benefits that may accrue to cancer patients is warranted. Additionally...

‣ Comparison of the effects of the novel vasodilator FK409 with those of nitroglycerin in isolated coronary artery of the dog.

Yamada, H.; Yoneyama, F.; Satoh, K.; Taira, N.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1991 Português
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1. The vasorelaxant effects of FK409, a new nitrovasodilator synthesized from a microbial product, were compared with those of nitroglycerin in isolated coronary artery rings of the dog contracted with U46619 (10(-7) M). 2. FK409 (10(-11)-10(-5) M) and nitroglycerin (10(-9)-10(-4) M) each produced a concentration-dependent relaxation. Comparison of EC50 values showed that FK409 was about 25 times more potent than nitroglycerin. 3. Submaximum concentrations of nitroglycerin (10(-6) M) and FK409 (3 x 10(-8) M) elevated guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels, effects associated with vasorelaxation. Adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were unaffected. 4. The concentration-relaxation curves for nitroglycerin and FK409 were shifted to the right by methylene blue (3 x 10(-6) - 3 x 10(-5) M), an inhibitor of soluble guanylate cyclase, and to the left by M&B22,948 (3 x 10(-6) - 3 x 10(-5) M), an inhibitor of cyclic GMP phosphodiesterase. 5. After exposure of coronary arteries to the maximally-effective concentration of nitroglycerin (10(-4) M), the mean EC50 value of FK409 did not change significantly, although that of nitroglycerin increased about 60 fold. After exposure to the maximally-effective concentration of FK409 (10(-5) M)...

‣ Sublingual Nitroglycerin Administration in Coronary Computed Tomography Angiography: a Systematic Review

Takx, Richard A. P.; Suchá, Dominika; Park, Jakob; Leiner, Tim; Hoffmann, Udo
Fonte: Springer Berlin Heidelberg Publicador: Springer Berlin Heidelberg
Tipo: Artigo de Revista Científica
Português
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Objective: To systematically investigate the literature for the influence of sublingual nitroglycerin administration on coronary diameter, the number of evaluable segments, image quality, heart rate and blood pressure, and diagnostic accuracy of coronary computed tomography (CT) angiography. Methods: A systematic search was performed in PubMed, EMBASE and Web of Science. The studies were evaluated for the effect of sublingual nitroglycerin on coronary artery diameter, evaluable segments, objective and subjective image quality, systemic physiological effects and diagnostic accuracy. Due to the heterogeneous reporting of outcome measures, a narrative synthesis was applied. Results: Of the 217 studies identified, nine met the inclusion criteria: seven reported on the effect of nitroglycerin on coronary artery diameter, six on evaluable segments, four on image quality, five on systemic physiological effects and two on diagnostic accuracy. Sublingual nitroglycerin administration resulted in an improved evaluation of more coronary segments, in particular, in smaller coronary branches, better image quality and improved diagnostic accuracy. Side effects were mild and were alleviated without medical intervention. Conclusion: Sublingual nitroglycerin improves the coronary diameter...