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At least 469 records · Page 26Linked to original sources
PubMed2003

Endothelial protection by pentaerithrityl trinitrate: bilirubin and carbon monoxide as possible mediators.

Pentaerithrityl tetranitrate (PETN) is a long-acting donor of nitric oxide (NO) and has recently been characterized as an antianginal agent that, in contrast with other nitric acid esters, does not induce oxidative stress and is therefore free of tolerance. Moreover, animal experiments have revealed that PETN actively reduces oxygen radical formation in vivoand specifically prevents atherogenesis and endothelial dysfunction. Because heme oxygenase-1 (HO-1) has been described as an antiatherogenic and cytoprotective gene in the endothelium, our aim was to investigate the effect of the active PETN metabolite pentaerithrityl trinitrate (PETriN) on HO-1 expression and catalytic activity in endothelial cells. Endothelial cells derived from human umbilical vein were incubated with PETriN (0.01-1 mM) for 8 hr. PETriN increased HO-1 mRNA and protein levels in a concentration-dependent fashion up to 3-fold over basal levels. Elevation of HO-1 protein was accompanied by a marked increase in catalytic activity of the enzyme as reflected by enhanced formation of both carbon monoxide and the endogenous antioxidant, bilirubin. Pretreatment of endothelial cells with PETriN or bilirubin at low micromolar concentrations protected endothelial cells from hydrogen peroxide-mediated toxicity. HO-1 induction and endothelial protection by PETriN were not mimicked by isosorbide dinitrate, another long-acting nitrate. The present study demonstrates that the active PETN metabolite, PETriN, stimulates mRNA and protein expression as well as enzymatic activity of the antioxidant defense protein, HO-1, in endothelial cells. Increased HO-1 expression and ensuing formation of bilirubin and carbon monoxide may contribute to and explain the specific antioxidant and antiatherogenic actions of PETN.

Animals↗
PubMed2006

Mitochondrial oxidative stress and nitrate tolerance--comparison of nitroglycerin and pentaerithrityl tetranitrate in Mn-SOD+/- mice.

BACKGROUND: Chronic therapy with nitroglycerin (GTN) results in a rapid development of nitrate tolerance which is associated with an increased production of reactive oxygen species (ROS). According to recent studies, mitochondrial ROS formation and oxidative inactivation of the organic nitrate bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2) play an important role for the development of nitrate and cross-tolerance. METHODS: Tolerance was induced by infusion of wild type (WT) and heterozygous manganese superoxide dismutase mice (Mn-SOD+/-) with ethanolic solution of GTN (12.5 mug/min/kg for 4 d). For comparison, the tolerance-free pentaerithrityl tetranitrate (PETN, 17.5 mug/min/kg for 4 d) was infused in DMSO. Vascular reactivity was measured by isometric tension studies of isolated aortic rings. ROS formation and aldehyde dehydrogenase (ALDH-2) activity was measured in isolated heart mitochondria. RESULTS: Chronic GTN infusion lead to impaired vascular responses to GTN and acetylcholine (ACh), increased the ROS formation in mitochondria and decreased ALDH-2 activity in Mn-SOD+/- mice. In contrast, PETN infusion did not increase mitochondrial ROS formation, did not decrease ALDH-2 activity and accordingly did not lead to tolerance and cross-tolerance in Mn-SOD+/- mice. PETN but not GTN increased heme oxygenase-1 mRNA in EA.hy 926 cells and bilirubin efficiently scavenged GTN-derived ROS. CONCLUSION: Chronic GTN infusion stimulates mitochondrial ROS production which is an important mechanism leading to tolerance and cross-tolerance. The tetranitrate PETN is devoid of mitochondrial oxidative stress induction and according to the present animal study as well as numerous previous clinical studies can be used without limitations due to tolerance and cross-tolerance.

Acetylcholine↗
PubMed2005

Standoff detection of high explosive materials at 50 meters in ambient light conditions using a small Raman instrument.

We have designed and demonstrated a standoff Raman system for detecting high explosive materials at distances up to 50 meters in ambient light conditions. In the system, light is collected using an 8-in. Schmidt-Cassegrain telescope fiber-coupled to an f/1.8 spectrograph with a gated intensified charge-coupled device (ICCD) detector. A frequency-doubled Nd : YAG (532 nm) pulsed (10 Hz) laser is used as the excitation source for measuring remote spectra of samples containing up to 8% explosive materials. The explosives RDX, TNT, and PETN as well as nitrate- and chlorate-containing materials were used to evaluate the performance of the system with samples placed at distances of 27 and 50 meters. Laser power studies were performed to determine the effects of laser heating and photodegradation on the samples. Raman signal levels were found to increase linearly with increasing laser energy up to approximately 3 x 10(6) W/cm2 for all samples except TNT, which showed some evidence of photo- or thermal degradation at higher laser power densities. Detector gate width studies showed that Raman spectra could be acquired in high levels of ambient light using a 10 microsecond gate width.

Environmental Monitoring↗
PubMed1998

Clinical pharmacokinetics of vasodilators. Part II.

Stimulating cardiac beta 1-adrenoceptors with oxyfedrine causes dilatation of coronary vessels and positive inotropic effects on the myocardium. beta 1-adrenergic agonists increase coronary blood flow in nonstenotic and stenotic vessels. The main indication for the use of the phosphodiesterase inhibitors pamrinone, mirinone, enoximone and piroximone is acute treatment of severe congestive heart failure. Theophylline is indicated for the treatment of asthma, chronic obstructive pulmonary disease, apnea in preterm infants ans sleep apnea syndrome. Severe arterial occlusive disease associated with atherosclerosis can be beneficially affected by elcosanoids. These drugs must be administered parenterally and have a half-life of only a few minutes. Sublingual or buccal preparations of nitrates are the only prompt method (within 1 or 2 min) of terminating anginal pain, except for biting nifedipine capsules. The short half-life (about 2.5 min) of nitroglycerin (glyceryl trinitrate) makes long term therapy impossible. Tolerance is a problem encountered with longer-acting nitric oxide donors. Knowledge of the pharmacokinetic properties of vasodilating drugs can prevent a too sudden and severe blood pressure decrease in patients with chronic hypertension. In considering the administration of a second dose, or another drug, the time necessary for the initially administered drug to reach maximal efficacy should be taken into account. In hypertensive emergencies urapidil, sodium nitroprusside, nitroglycerin, hydralazine and phentolamine are the drugs of choice, with the addition of beta-blockers during catecholamine crisis or dissecting aortic aneurysm. Childhood hypertension is most often treated with angiotensin-converting enzyme (ACE) inhibitors or calcium antagonists, primarily nifedipine. Because of the teratogenic risk involved with ACE inhibitors, extreme caution must be exercised when prescribing for adolescent females. The propagation of health benefits to breast-fed infants, combined with more women delaying pregnancy until their fourth decade, has entailed an increase in the need for hypertension management during lactation. Low dose hydrochlorothiazide, propranolol, nifedipine and enalapril or captopril do not pose enough of a risk of preclude breastfeeding in this group. The most frequently used antihypertensive agents during pregnancy are methyldopa, labetalol and calcium channel antagonists. Methyldopa and beta-blockers are the drugs of choice for treating mild to moderate hypertension. Prazosin and hydralazine are used to treat moderate to severe hypertension and hydralazine, urapidil or labetalol are used to treat hypertensive emergencies. The use of overly aggressive antihypertensive therapy during pregnancy should be avoided so that adequate uteroplacental blood flow is maintained. Methyldopa is the only drug accepted for use during the first trimester of pregnancy.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

[Comparison of the antiangina pectoris action of 2 coronary vasodilators].

Twenty four patients were studied: 7 males and 17 females, with an average age of 56 plus and minus 6.93 years, with a main diagnosis of ischaemic heart disease and with an average of at least 7 angina attacks per week. The anti-angina effect of 2 drugs, dipridamol and pentaeritritol was compared using the random double blind technique on parallel groups which were comparable. Pentaertritol administered for 4 weeks reduced, with a statistical significance (P 0.01), the average number of angina attacks of the group, as well as with taking nitroglicerine tablets. The number of pain free days was increased from 1.5 per week to 5.5 in 7 days. The effort capacity of the patients increased (P 0.01), and also the degree of elevation of the ST segment during and post effort. The changes obtained in these same areas with dipiridamol had no statistical significance.

Adult↗
PubMed1979

Contact dermatitis due to nitroglycerin ointment.

Topical nitroglycerin ointment is among the most effective long-acting vasodilators currently available. We report two cases of contact dermatitis in which patch testing showed allergy to nitroglycerin-containing compounds. The severity of this dermatitis necessitated the discontinuation of topical nitroglycerin therapy in both patients. A potent corticosteroid cream applied once to previous nitroglycerin application sites prevented or minimized this dermatitis and enabled continuation of topical nitroglycerin therapy. Contact dermatitis due to topical nitroglycerin preparations may be more common than is presently realized.

Aged↗
PubMed1975

[Treatment of coronary insufficiency with a combination of 2 nitro-derivatives. Controlled pluricentric clinical trial].

The effectiveness of an association of two nitroderivatives (Stenodylate) was compared with that of its individual components. The association was found more effective in the relief of both subjective and objective symptoms in 118 cases of coronary insufficiency. In addition, it was well tolerated and would appear to be indicated in the management of this form.

Adult↗
PubMed2001

[Beneficial effects of exogenous NO donors on morphologic changes induced by long-term administration of NO synthase blockers].

Nitric oxide represents an important mediator which is involved in a variety of cardiovascular functions. The goal of this work was to study the effect of long term NO synthase inhibition on the structure of conduit arteries. The second objective of this work was to determine whether changes in conduit arteries evoked by long term NO synthase inhibition could be prevented by concomitant delivery of exogenous NO. Two independent experiments (A, B) were performed. Both consisted of three groups of 10-week-old Wistar rats: (1) controls, (2) treated by L-NC-nitroarginine methyl ester (L-NAME) in water (50 mg/kg), and (3) in experiment A treated by L-NAME (50 mg/kg in water) + pentaerythrityetetranitrate (PETN) (2 x 50 mg/kg, using gavage), (3) in experiment B treated by L-NAME (50 mg/kg in water) + molsidomine (2 x 50 mg/kg, using gavage). Blood pressure (BP) was measured in all groups by the tail plethysmogrphic method. After 6 weeks the rats were killed and perfused by the glutaraldehyde fixative under the pressure equal to the control systolic blood pressure of 120 mmHg. Thoracic aorta, carotid artery and coronary artery were processed according to the standard electron microscopy procedure. Wall thickness (WT), cross sectional area (CSA), and inner diameter (ID) of the arteries were measured in light microscopy. A significant increase in BP, WT, CSA and WT/ID ratio (all p < 0.01) were observed after L-NAME administration in arteries, except of WT/ID in the coronary artery in experiment A where the increase was not significant. ID changed not. Administration of PETN or molsidomine to L-NAME treated rats resulted in a significant decrease in BP, WT, and CSA. The decrease in WT/ID in coronary arteries was present however not significant in experiment A. The inner diameter was significantly increased only in the thoracic aorta in experiment A. In summary, long term NO synthase inhibition evoked considerable morphological changes in the arterial wall of conduit arteries. The replacement of endogenous NO deficiency using exogenous NO donors resulted in a considerably beneficial effect in all parameters studied. (Fig. 4, Ref. 54.)

Animals↗
PubMed2002

[Electrochemical reduction of pentaerythrityltetranitrate (PETN) and metabolites].

The reduction-cascade of PETN is described as a combination of cyclic-voltammetric measurements and analytical results together with synthesis of PETN-metabolites; furthermore the electroreduction of pentaerythityldinitrate (PEDN) in the presence and absence of cystine as well as cystine and electrogenerated superoxide-radicalanions to elucidate the interaction of PETN with thiol-species. PETN was recognized as precursor for a initial radicalic process, followed by intermediate formation of pentaerythityltrinitratealdehyde (PENA) inside a self-reducing nitrate-system with NO as final product, which may explain its special position in comparison with other pharmaceutically applied nitratestructures. It could be proved, that a cystine-pool reacts as a selective moderator inside the reduction of PEDN without being interfered by O2.-, yielding pentaerythitylmononitrate (PEMN) meanwhile in the absence of cystine only pentaerythrite (PE) is formed.

Cystine↗