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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1998-2-3
pubmed:abstractText
The goal of the present study was to determine the effects of chronic beta-adrenergic receptor stimulation with isoproterenol (ISO) on cardiac tissue, systemic trophic changes and on beta-adrenergic receptor desensitization in mice. Mice (n=36) received continuous ISO (30 microg/g/day) via osmotic minipump for 13 days. Left ventricle (LV)/body weight (BW) ratio was increased by 27% in ISO v control (CON) mice. The extent of cardiac hypertrophy induced by chronic ISO was offset in part by concomitant increases in body weight, which were greater in ISO than CON mice (22 v 8%), and occurred with increases in both muscle mass and brown fat to BW ratios. Histological analysis of mice revealed a three-fold increase in subendocardial interstitial connective tissue with no evidence of acute cellular necrosis or chronic inflammation. Acute i.v. ISO challenges induced dose-dependent increases in LV fractional shortening (FS) and ejection fraction (EF) using echocardiography (9 MHz), which were attenuated after chronic ISO, i.e. physiological desensitization was observed. Cellular mechanisms of beta-adrenergic receptor desensitization included decreases in beta-adrenergic receptor density (-49%) and decreased basal (-45%) and ISO-stimulated (-61%) adenylyl cyclase activities. Lesser decreases in forskolin-stimulated adenylyl cyclase activity (-16%) and adenylyl cyclase mRNA levels for both type V (-17%) and type VI (-23%) isoforms were observed following chronic ISO. Thus, chronic ISO (30 microg/g/day) induced cardiac hypertrophy without cellular necrosis, increased weight gain and clear physiological desensitization in mice, with more extensive biochemical mechanisms than expected from simple catecholamine-specific (homologous) desensitization.
pubmed:grant
pubmed:keyword
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2828
pubmed:author
pubmed:copyrightInfo
Copyright 1997 Academic Press Limited.
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2735-46
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Effects of chronic beta-adrenergic receptor stimulation in mice.
pubmed:affiliation
Cardiovascular and Pulmonary Research Institute, Allegheny University of the Health Sciences, Pittsburgh, PA 15212, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.