| Activity of a new hydrogen sulfide-releasing aspirin (ACS14) on pathological cardiovascular alterations induced by glutathione depletion in rats. | |
| | |
MedLine Citation:
|
PMID: 20826133 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
We investigated the effects of the hydrogen sulfide (H₂S)-releasing derivatives of aspirin (ACS14) and salicylic acid (ACS21) in a rat model of metabolic syndrome induced by glutathione (GSH) depletion, causing hypertension and other pathological cardiovascular alterations. GSH depletion was induced in normal rats by the GSH-synthase inhibitor buthionine sulfoximine (BSO, 30 mmol/L day for seven days in the drinking water). Systolic blood pressure and heart rate were measured daily by the tail-cuff method, and plasma thromboxane B₂, 6-keto-prostaglandin F(2α), 8-isoprostane, GSH, insulin and glucose were determined at the end of the seven-day BSO schedule. In addition, ischemia/reperfusion-induced myocardial dysfunction and endothelial dysfunction were assayed on isolated heart and aortic rings, respectively. Unlike aspirin and salicylic acid, ACS14 and ACS21 reduced BSO-induced hypertension, also lowering plasma levels of thromboxane B₂, 8-isoprostane and insulin, while GSH remained in the control range. Neither ACS14 nor ACS21 caused gastric lesions. Both restored the endothelial dysfunction observed in aortic rings from BSO-treated rats, and in ischemia/reperfusion experiments they lowered left ventricular end-diastolic pressure, consequently improving the developed pressure and the maximum rise and fall of left ventricular pressure. Together with this improvement of heart mechanics there were reductions in the activity of creatine kinase and lactate dehydrogenase in the cardiac perfusate. This implies that H₂S released by both ACS14 and ACS21 was involved in protecting the heart from ischemia/reperfusion, and significantly limited vascular endothelial dysfunction in aortic tissue and the related hypertension. |
| | |
Authors:
|
Giuseppe Rossoni; Barbara Manfredi; Valerio Tazzari; Anna Sparatore; Silvio Trivulzio; Piero Del Soldato; Ferruccio Berti |
Related Documents
:
|
9515043 - Ischemic preconditioning: effects on ph, na and ca in newborn rabbit hearts during isch... 8498583 - Albumin-binding superoxide dismutase with a prolonged half-life reduces reperfusion bra... 4830233 - Digitalis-induced increase in aortic regurgitation and the contrasting effect of glucag... |
Publication Detail:
|
Type: Journal Article Date: 2010-09-15 |
Journal Detail:
|
Title: European journal of pharmacology Volume: 648 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2010 Dec |
Date Detail:
|
Created Date: 2010-10-12 Completed Date: 2011-01-21 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 139-45 Citation Subset: IM |
Copyright Information:
|
Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
|
Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy. giuseppe.rossoni@unimi.it |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Aorta / drug effects, metabolism, pathology, physiopathology Aspirin / analogs & derivatives, chemistry*, pharmacology*, therapeutic use Blood Pressure / drug effects Consciousness Creatine Kinase / metabolism Endothelium, Vascular / drug effects, physiopathology Gastric Mucosa / drug effects Glutathione / deficiency*, metabolism Heart / drug effects*, physiopathology Heart Rate / drug effects Hydrogen Sulfide / chemistry* L-Lactate Dehydrogenase / metabolism Male Malondialdehyde / metabolism Metabolic Syndrome X / chemically induced, drug therapy, metabolism, physiopathology Myocardial Reperfusion Injury / metabolism, physiopathology Myocardium / metabolism* Oxidative Stress / drug effects Rats Rats, Wistar Vasodilation / drug effects |
| Chemical | |
Reg. No./Substance:
|
50-78-2/Aspirin; 542-78-9/Malondialdehyde; 70-18-8/Glutathione; 7783-06-4/Hydrogen Sulfide; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.7.3.2/Creatine Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Metabotropic glutamate receptor mGlu2 is resistant to homologous agonist-induced desensitization but...
Next Document: Chronic lithium treatment protects the rat kidney against ischemia/reperfusion injury: the role of n...