Tolerance to nitroglycerin induced by isosorbide-5-mononitrate infusion invivo

Citation
T. Manabe et al., Tolerance to nitroglycerin induced by isosorbide-5-mononitrate infusion invivo, BIOL PHAR B, 24(12), 2001, pp. 1370-1372
Citations number
17
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOLOGICAL & PHARMACEUTICAL BULLETIN
ISSN journal
0918-6158 → ACNP
Volume
24
Issue
12
Year of publication
2001
Pages
1370 - 1372
Database
ISI
SICI code
0918-6158(200112)24:12<1370:TTNIBI>2.0.ZU;2-P
Abstract
We examined the development of tolerance to nitroglycerin (glyceryl trinitr ate, GTN) in the rat when isosorbide-5-mononitrate (ISMN) or GTN was contin uously infused. Under pentobarbital anesthesia (60 mg/kg, i.p.), mean arter ial blood pressure was measured via the left common carotid artery. Bolus i njection of ISMN (0.25-250 mg/kg) and GTN (0.25 mug/kg-2.5 mg/kg) was made into the right external jugular vein. ISMN (2.5 mg/h/rat for 7 d). GTN (1.3 mug/h/rat for 7 d), or GTN (0.2 mg/h/rat for 3 d) was infused continuously using an osmotic pump embedded subcutaneously. Bolus injection of ISMN and GTN decreased arterial blood pressure in a dose-dependent manner. The hypo tensive effect of ISMN was 2000 times less potent than that of GTN. The GTN -induced hypotensive effect was not affected after continuous infusion of I SMN, whereas it was attenuated after continuous infusion of GTN at either d ose. Chronic treatment with ISMN does not induce GTN tolerance as easily as treatment with GTN.