Document Detail


Positive inotropic and negative lusitropic effects of endothelin receptor agonism in vivo.
MedLine Citation:
PMID:  15951343     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The endothelin (ET) system is involved in the regulation of myocardial function in health as well as in several diseases, such as congestive heart failure, myocardial infarction, and septic myocardial depression. Conflicting results have been reported regarding the acute contractile properties of ET-1. We therefore investigated the effects of intracoronary infusions of ET-1 and of the selective ET(B) receptor-selective agonist sarafotoxin 6c with increasing doses in anesthetized pigs. Myocardial effects were measured through analysis of the left ventricular pressure-volume relationship. ET-1 elicited increases in the myocardial contractile status (end-systolic elastance value of 0.94 +/- 0.11 to 1.48 +/- 0.23 and preload recruitable stroke work value of 68.7 +/- 4.7 to 83.4 +/- 7.2) that appear to be mediated through ET(A) receptors, whereas impairment in left ventricular isovolumic relaxation (tau = 41.5 +/- 1.4 to 58.1 +/- 5.0 and t(1/2) = 23.0 +/- 0.7 to 30.9 +/- 2.6, where tau is the time constant for pressure decay and t(1/2) is the half-time for pressure decay) was ET(B) receptor dependent. In addition, intravenous administration of ET-1 impaired ventricular relaxation but had no effect on contractility. Intracoronary sarafotoxin 6c administration caused impairments in left ventricular relaxation (tau from 43.3 +/- 1.8 to 54.4 +/- 3.4) as well as coronary vasoconstriction. In conclusion, ET-1 elicits positive inotropic and negative lusitropic myocardial effects in a pig model, possibly resulting from ET(A) and ET(B) receptor activation, respectively.
Authors:
D Konrad; A Oldner; M Wanecek; A Rudehill; E Weitzberg; B Biber; G Johansson; S Häggmark; M Haney
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-06-10
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  289     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-09-15     Completed Date:  2005-10-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1702-9     Citation Subset:  IM    
Affiliation:
Department of Surgical Sciences, Section for Anaesthesiology and Intensive Care, Karolinska Institute, Stockholm, Sweden. david.konrad@kirurgi.ki.se
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MeSH Terms
Descriptor/Qualifier:
Anesthesia
Animals
Cardiotonic Agents / pharmacology*
Coronary Circulation / drug effects
Diastole / drug effects
Endothelin-1 / blood,  pharmacology*
Female
Heart / drug effects*,  physiology
Injections, Intravenous
Myocardial Contraction / drug effects
Oxygen / metabolism
Receptor, Endothelin B / antagonists & inhibitors
Receptors, Endothelin / agonists*
Sus scrofa
Vasoconstrictor Agents / pharmacology
Ventricular Pressure / drug effects
Viper Venoms / pharmacology
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Endothelin-1; 0/Receptor, Endothelin B; 0/Receptors, Endothelin; 0/Vasoconstrictor Agents; 0/Viper Venoms; 0/sarafotoxins s6; 7782-44-7/Oxygen

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


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