Document Detail


The effects of phosphoramidon on the regional haemodynamic responses to human proendothelin [1-38] in conscious rats.
MedLine Citation:
PMID:  1912989     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Cardiovascular responses to human proendothelin [1-38], in the absence and presence of phosphoramidon, were studied in conscious Long Evans rats, chronically instrumented for the continuous recording of heart rate, systemic arterial blood pressure and renal, mesenteric and hindquarters blood flows. 2. A dose of 0.1 nmol kg-1 human proendothelin [1-38] caused a slight pressor effect (maximum 5 +/- 2 mmHg), but a clear bradycardia (maximum -29 +/- 7 beats min-1). Renal haemodynamics were unchanged but there was mesenteric vasoconstriction and a vasodilation followed by a vasoconstriction in the hindquarters. 3. A dose of 1.0 nmol kg-1 human proendothelin [1-38] caused a gradual hypertension (maximum 42 +/- 4 mmHg at 10 min) and a profound bradycardia (-149 +/- 10 beats min-1 at 30 min). There were gradual but marked, renal and hindquarters vasoconstrictions, whereas there was a substantial mesenteric vasoconstriction that was relatively rapid in onset. 4. In 2 animals, administration of human proendothelin [1-38] at a dose of 10 nmol kg-1 caused an initial hypotension followed by a rapidly-developing pressor effect; there were renal and mesenteric vasoconstrictions and vasodilatation followed by vasoconstriction in the hindquarters. These changes were very similar to those seen following injection of endothelin-1 (0.1 nmol kg-1). 5. Phosphoramidon (2 mumol kg-1) had no cardiovascular effects itself and it did not affect significantly the pressor or mesenteric vasoconstrictor effects of human proendothelin [1-38], but it reduced the bradycardia and renal and hindquarters vasoconstrictor responses. A higher dose of phosphoramidon (lOnmolkg-') caused significant attenuation of all the responses to human proendothelin [1-38], but a substantial mesenteric vasoconstrictor response still occurred under these conditions. 6 The results are consistent with the involvement of phosphoramidon-sensitive enzyme systems in the conversion of human proendothelin [1-38] to endothelin-1 in vivo. In addition, considering the different patterns of responses to human proendothelin [1-38] in the effector tissues studied (heart, and renal, mesenteric and hindquarters vascular beds), and the differential degrees of inhibition of them by phosphoramidon, it is likely that the effects of human proendothelin [1-38] were due to its local (rather than systemic) conversion to endothelin-1 by processes with differing degrees of susceptibility to phosphoramidon.
Authors:
S M Gardiner; A M Compton; P A Kemp; T Bennett
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  103     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1991 Aug 
Date Detail:
Created Date:  1991-10-31     Completed Date:  1991-10-31     Revised Date:  2010-05-19    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2009-15     Citation Subset:  IM    
Affiliation:
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham.
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MeSH Terms
Descriptor/Qualifier:
Animals
Doppler Effect
Endothelin-1
Endothelins / administration & dosage,  pharmacology*
Glycopeptides / pharmacology*
Hemodynamics / drug effects*
Humans
Kidney / drug effects
Male
Mesenteric Veins / drug effects
Protein Precursors / administration & dosage,  pharmacology*
Rats
Rats, Inbred Strains
Regional Blood Flow / drug effects
Chemical
Reg. No./Substance:
0/Endothelin-1; 0/Endothelins; 0/Glycopeptides; 0/Protein Precursors; 36357-77-4/phosphoramidon
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