Document Detail

Tolerance to the increase in coronary blood flow induced by KRN2391.
MedLine Citation:
PMID:  1463369     Owner:  NLM     Status:  MEDLINE    
We examined whether KRN2391, isosorbide dinitrate and nitroglycerin induced tolerance in coronary arteries. Intracoronary arterial administration of KRN2391 (1 microgram), isosorbide dinitrate (30 micrograms) or nitroglycerin (3 micrograms) produced equipotent coronary vasodilatation. Development of tolerance was determined by whether the increase in coronary blood flow, caused by intracoronary arterial administration of these drugs, was attenuated by intravenous infusion of KRN2391, isosorbide dinitrate or nitroglycerin. The increase in coronary blood flow, caused by intracoronary arterial administration of KRN2391 was not affected by intravenous infusion of KRN2391 (0.3 or 1 micrograms/kg/min), isosorbide dinitrate (30 or 100 micrograms/kg/min) or nitroglycerin (1 or 3 micrograms/kg/min). The increase in coronary blood flow, caused by intracoronary arterial administration of isosorbide dinitrate or nitroglycerin, was significantly diminished by intravenous infusion of isosorbide dinitrate and nitroglycerin, but was unaffected by intravenous infusion of KRN2391. The present results suggest that KRN2391 does not induce acute tolerance by itself or cross-tolerance between KRN2391 and other nitrates.
S Kaneta; Y Jinno; K Harada; H Fukushima; N Ogawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Archives internationales de pharmacodynamie et de thérapie     Volume:  318     ISSN:  0003-9780     ISO Abbreviation:  Arch Int Pharmacodyn Ther     Publication Date:    1992 Jul-Aug
Date Detail:
Created Date:  1993-01-14     Completed Date:  1993-01-14     Revised Date:  2012-01-12    
Medline Journal Info:
Nlm Unique ID:  0405353     Medline TA:  Arch Int Pharmacodyn Ther     Country:  BELGIUM    
Other Details:
Languages:  eng     Pagination:  21-35     Citation Subset:  IM    
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
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MeSH Terms
Coronary Circulation / drug effects*
Dose-Response Relationship, Drug
Drug Synergism
Drug Tolerance
Hemodynamics / drug effects
Infusions, Intravenous
Isosorbide Dinitrate / administration & dosage,  pharmacology
Nitroglycerin / administration & dosage,  pharmacology
Pharmaceutical Vehicles
Pyridines / administration & dosage,  pharmacology*
Vasodilator Agents / administration & dosage,  pharmacology*
Reg. No./Substance:
0/Pharmaceutical Vehicles; 0/Pyridines; 0/Vasodilator Agents; 134431-49-5/N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; 55-63-0/Nitroglycerin; 87-33-2/Isosorbide Dinitrate

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