Search results for "Isosorbide dinitrate"
showing 10 items of 12 documents
Pentaerythrityl Tetranitrate and Nitroglycerin, but not Isosorbide Mononitrate, Prevent Endothelial Dysfunction Induced by Ischemia and Reperfusion
2007
Background— Short term exposure to nitroglycerin (GTN) has protective properties that are similar to ischemic preconditioning. Whether other organic nitrates such as pentaerithrityl tetranitrate (PETN) and isosorbide mononitrate (ISMN) have similar protective effects has not been explored. Methods and Results— In a randomized, parallel, double blind, controlled trial, 37 healthy young volunteers received no therapy (n=10), transdermal GTN 1.2 mg for 2 hours (n=9), PETN 80 mg (n=9), or ISMN 40 mg (n=9). Twenty-four hours later, endothelium-dependent flow-mediated vasodilation (FMD) was measured before and after local exposure to ischemia and reperfusion (IR). In the no therapy group, IR blu…
Vascular Dysfunction in Experimental Diabetes Is Improved by Pentaerithrityl Tetranitrate but Not Isosorbide-5-Mononitrate Therapy
2011
OBJECTIVE Diabetes is associated with vascular oxidative stress, activation of NADPH oxidase, and uncoupling of nitric oxide (NO) synthase (endothelial NO synthase [eNOS]). Pentaerithrityl tetranitrate (PETN) is an organic nitrate with potent antioxidant properties via induction of heme oxygenase-1 (HO-1). We tested whether treatment with PETN improves vascular dysfunction in the setting of experimental diabetes. RESEARCH DESIGN AND METHODS After induction of hyperglycemia by streptozotocin (STZ) injection (60 mg/kg i.v.), PETN (15 mg/kg/day p.o.) or isosorbide-5-mononitrate (ISMN; 75 mg/kg/day p.o.) was fed to Wistar rats for 7 weeks. Oxidative stress was assessed by optical methods and o…
Isosorbide dinitrate: pharmacokinetics after intravenous administration.
1982
Isosorbide dinitrate (ISDN) is an important organic nitrate found therapeutically useful in its sublingual and oral forms in various cardiovascular diseases such as angina pectoris (1) and congestive heart failure (2). Recently Distante et al. (3) showed that an intravenous infusion of this drug, at 0.021–0.083 mg/min is also effective in managing unstable angina. The availability of an intravenous dosage form of ISDN not only affords the opportunity to characterize the pharmacokinetics of this drug after this particular mode of therapy, but also gives the possibility of assessing the bio-availability of this drug after other (e.g., oral) routes of administration in patients. This latter po…
The ineffectiveness of the NO-cyclic GMP signaling pathway in the atrial myocardium
1995
1. This study was performed to determine whether nitric oxide (NO) has direct effects on force of contraction (Fc) in atrial myocardium from rats, rabbits, guinea-pigs, frogs, and man. 2. Glyceryl trinitrate, isosorbide dinitrate, 3-morpholino-sydnonimine hydrochloride (SIN-1), and S-nitroso-N-acetylpenicillamine (SNAP) did not significantly reduce Fc in the various preparations investigated, either given alone or after stimulation of alpha- or beta-adrenoceptors. 3. SNAP did not change the time course of contractions in rat, guinea-pig and human preparations. 4. 8-Bromo-guanosine-3':5'-cyclic monophosphate (8-Br-cyclic GMP) produced a negative inotropic effect in rat, guinea-pig and human …
Hydralazine is a powerful inhibitor of peroxynitrite formation as a possible explanation for its beneficial effects on prognosis in patients with con…
2005
The hemodynamic and anti-ischemic effects of nitroglycerin (GTN) are rapidly blunted as a result of the development of nitrate tolerance. Hydralazine has been shown to prevent tolerance in experimental and clinical studies, all of which may be at least in part secondary to antioxidant properties of this compound. The antioxidant effects of hydralazine were tested in cell free systems, cultured smooth muscle cells, isolated mitochondria, and isolated vessels. Inhibitory effects on the formation of superoxide and/or peroxynitrite formation were tested using lucigenin and L-012 enhanced chemiluminescence as well as DHE-fluorescence. The peroxynitrite scavenging properties were also assessed by…
Hepatic extraction of isosorbide dinitrate in cardiac patients
1983
Hepatic extraction of organic nitrates, including that of isosorbide dinitrate (ISDN), has been thought to be nearly complete in man but has never been directly measured. We examined the time course of plasma ISDN and metabolite concentrations in arterial and hepatic venous blood in four cardiac patients receiving an intravenous ISDN infusion. Apparent hepatic extraction of ISDN was high (90%) at the beginning of infusion but fell to about 44% 1 hr after termination of infusion. The decrease in ISDN concentration gradient across the liver correlates with an increase in plasma isosorbide-5-mononitrate concentration, but a cause-and-effect relationship resulting from metabolite inhibition can…
Chronic Therapy With Isosorbide-5-Mononitrate Causes Endothelial Dysfunction, Oxidative Stress and a Marked Increase in Vascular Endothelin-1 Express…
2011
Aims Isosorbide-5-mononitrate (ISMN) is one of the most frequently used compounds in the treatment of coronary artery disease predominantly in the USA. However, ISMN was reported to induce endothelial dysfunction, which was corrected by vitamin C pointing to a crucial role of reactive oxygen species (ROS) in causing this phenomenon. We sought to elucidate the mechanism how ISMN causes endothelial dysfunction and oxidative stress in vascular tissue. Methods and results Male Wistar rats ( n = 69 in total) were treated with ISMN (75 mg/kg/day) or placebo for 7 days. Endothelin (ET) expression was determined by immunohistochemistry in aortic sections. Isosorbide-5-mononitrate infusion caused si…
Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress
2015
Abstract Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3′,-5′-monophosphate (cGMP) levels lead to an activation of…
Characterization of the Antioxidant Properties of Pentaerithrityl Tetranitrate (PETN)-Induction of the Intrinsic Antioxidative System Heme Oxygenase-…
2009
Organic nitrates are among the oldest and yet most commonly employed drugs in the chronic therapy of coronary artery disease and congestive heart failure. While they have long been used in clinical practise, our understanding of their mechanism of action and of their side effects remains incomplete. To date, the most commonly employed nitrates are isosorbide mononitrate (ISMN), isosorbide dinitrate (ISDN), and nitroglycerin (GTN). Another nitrate, pentaerithrityl tetranitrate (PETN), has long been employed in eastern European countries and is currently being reintroduced also in western countries. So far, PETN is the only organic nitrate in clinical use, which is devoid of induction of oxid…