Document Detail


Increase in the basal tone of guinea pig thoracic aorta induced by ouabain is inhibited by spironolactone canrenone and potassium canrenoate.
MedLine Citation:
PMID:  8891876     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Guinea pig aorta rings repeatedly stimulated with phenylephrine (1 microM) in the presence of Krebs solution containing ouabain (0.8 microM) or low K+ (0.5 mM) concentration produced an increase in basal tone. This effect is due to an increase in intracellular Ca2+ as a consequence of Na(+)-K+ATPase pump inhibition induced by receptorial (ouabain) or ion imbalance (low K+) mechanism. We investigated the effect of spironolactone and its metabolites canrenone and potassium canrenoate on the increase in basal tone of guinea pig aorta rings. Spironolactone, canrenone, and potassium canrenoate, in a concentration-dependent manner (3-30 microM), inhibited the increase in basal tone induced by ouabain, most likely acting as antagonist for ouabain binding site on Na(+)-K+ATPase pump. Indeed, this effect appears to be a feature of these drugs since structurally related drugs, such as aldosterone and hydrocortisone, were ineffective. Conversely, all the drugs tested reduced, to a certain degree, the increase in basal tone produced by low K+ Krebs solution, implying that this could be a non-specific effect. Our results may indicate that spironolactone, canrenone, and potassium canrenoate act in hypertension by interfering with mechanisms in which an ouabain-like factor is involved.
Authors:
R Sorrentino; G Cirino; A Calignano; F Mancuso; L Sorrentino; G Andriuoli; A Pinto
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  28     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1997-03-24     Completed Date:  1997-03-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  519-25     Citation Subset:  IM    
Affiliation:
Department of Experimental Pharmacology, University of Naples Federico II, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta, Thoracic
Canrenoate Potassium / pharmacology*
Canrenone / analogs & derivatives,  pharmacology*
Cardiotonic Agents / pharmacology*
Guinea Pigs
Isotonic Solutions / pharmacology
Muscle, Smooth, Vascular / drug effects,  physiology
Ouabain / antagonists & inhibitors,  pharmacology*
Potassium / metabolism
Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
Spironolactone / pharmacology*
Vasoconstriction / drug effects*
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Isotonic Solutions; 0/Krebs-Ringer solution; 2181-04-6/Canrenoate Potassium; 52-01-7/Spironolactone; 630-60-4/Ouabain; 7440-09-7/Potassium; 976-71-6/Canrenone; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase

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


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