Document Detail

Effect of tolerance to glyceryl trinitrate on vascular responses in conscious rabbits.
MedLine Citation:
PMID:  1914247     Owner:  NLM     Status:  MEDLINE    
1. The effect of tolerance to glyceryl trinitrate (GTN) on vasodilator and vasoconstrictor responses was examined in conscious rabbits and isolated rabbit aortic rings. 2. In conscious rabbits, depressor responses to 5 min infusions of GTN (10-40 micrograms/kg per min intravenously (i.v.)), sodium nitroprusside (SNP, 5-20 micrograms/kg per min i.v.) and acetylcholine (ACh, 3-12 micrograms/kg per min i.v.) were examined before and after transdermal treatment with GTN (20 mg/48 h). GTN pretreatment significantly attenuated GTN-induced depressor responses, indicating the development of tolerance, but did not affect the reductions in arterial pressure induced by SNP or ACh. 3. Similarly, aortic rings taken from GTN pretreated rabbits exhibited tolerance to GTN but the relaxant responses to SNP or the calcium ionophore A23187 were not affected. In the aortic rings from GTN-tolerant rabbits contractile responses to serotonin or the thromboxane-mimetic U46619 were significantly attenuated, in contrast to the responses to the alpha 1-adrenoceptor agonist phenylephrine (PE) which were significantly enhanced. 4. Similarly, in conscious rabbits, PE-induced increases in arterial pressure and hindlimb vascular resistance were significantly enhanced by GTN pretreatment but the responses to the alpha 2-adrenoceptor agonist BHT 920 were unaffected. 5. In conclusion, tolerance to GTN does not affect endothelium-dependent vasodilatation but does cause a selective enhancement of alpha 1- but not alpha 2-adrenoceptor-mediated vasoconstriction.
Z Y Du; G J Dusting; O L Woodman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  18     ISSN:  0305-1870     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  1991 Jun 
Date Detail:
Created Date:  1991-11-08     Completed Date:  1991-11-08     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  439-47     Citation Subset:  IM    
Department of Pharmacology, University of Melbourne, Victoria, Australia.
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MeSH Terms
Administration, Cutaneous
Aorta, Thoracic / drug effects*,  physiology
Drug Tolerance / physiology
Endothelium, Vascular / drug effects*,  physiology
Hemodynamics / drug effects
Muscle Contraction / drug effects
Muscle Relaxation / drug effects
Nitroglycerin / pharmacology*
Vasoconstrictor Agents / pharmacology
Reg. No./Substance:
0/Vasoconstrictor Agents; 55-63-0/Nitroglycerin

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

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