Document Detail

Two possible mechanisms underlying nitrate tolerance in monkey coronary arteries.
MedLine Citation:
PMID:  11251637     Owner:  NLM     Status:  MEDLINE    
1. Previous studies using isolated arteries have demonstrated cross-tolerance between nitric oxide (NO) donors such as nitroglycerin (NTG) and sodium nitroprusside (SNP). However, it remains unclear whether the vasorelaxing effect of atrial natriuretic peptide (ANP), an activator of particulate guanylate cyclase, is affected by treatment with NO donors. To investigate the cross-tolerance and interactions between NTG and ANP in coronary vasorelaxant responses, we used two models of monkey coronary arterial strips (Macaca fuscata). 2. In one model, which was induced by a 1 h treatment with 4.4 x 10(-4) mol/L NTG followed by washout of the agent for 1 h, the vasorelaxing effects of subsequent NTG were markedly attenuated, whereas those of ANP and NO were not affected. These findings suggest that the development of NTG tolerance is associated with a biotransformation process from NTG to NO. In the other model, which did not include washout after exposure to 3 x 10(-6) mol/L NTG, the vasorelaxant responses to 10(-8) mol/L ANP (31.1+/-5.4 vs 5.1+/-2.1%, respectively; P < 0.001), 10(-6) mol/L NO (61.5+/-2.4 vs 29.5+/-8.5%, respectively; P < 0.001) and 10(-8) mol/L SNP (49.4+/-6.4 vs 8.0+/-2.0%, respectively; P < 0.001) were significantly attenuated. The concentration- response curve for 8-bromo-cGMP (8-Br-cGMP) was shifted to the right, whereas responses to papaverine and forskolin were unchanged. These findings suggest that an intracellular process that occurs after the synthesis of cGMP is responsible for this interaction. 3. As a mechanism of NTG tolerance, two possible processes may be impaired: (i) biotransformation from NTG to NO; and (ii) an intracellular process that occurs after the synthesis of cGMP.
T Omura; T Matsumoto; I Nakae; M Takahashi; M Kinoshita
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  28     ISSN:  0305-1870     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-03-19     Completed Date:  2001-07-12     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  259-65     Citation Subset:  IM    
First Department of Internal Medicine, Shiga University of Medical Science, Seta, Otsu, Japan.
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MeSH Terms
Atrial Natriuretic Factor / pharmacology*
Coronary Vessels / drug effects*,  metabolism
Cyclic GMP / metabolism
Drug Interactions
Drug Tolerance / physiology*
Nitrates / pharmacology
Nitric Oxide / metabolism,  pharmacology
Nitroglycerin / pharmacology*
Nitroprusside / pharmacology
Vasodilation / drug effects,  physiology
Vasodilator Agents / pharmacology*
Reg. No./Substance:
0/Nitrates; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 15078-28-1/Nitroprusside; 55-63-0/Nitroglycerin; 7665-99-8/Cyclic GMP; 85637-73-6/Atrial Natriuretic Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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