Document Detail


Downregulation of ANG II receptor is associated with compensated pressure-overload hypertrophy in the young dog.
MedLine Citation:
PMID:  11788426     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We studied the gradual onset of pressure overload (PO) induced by a mildly constricting aortic band in 8-wk-old puppies (n = 8) that increased to 98 +/- 11 mmHg at 9 mo. Left ventricular (LV) weight/body weight was increased in PO versus sham-operated littermate controls [8.11 +/- 0.60 (SE) vs. 4.46 +/- 0.38 g/kg, P < 0.001]. LV end-diastolic diameter, diastolic pressure, and fractional shortening did not differ in PO versus control dogs. There were no inducible arrhythmias in response to an aggressive electrophysiological stimulation protocol in PO dogs. Furthermore, isolated cardiomyocyte function did not differ between control and PO dogs. LV angiotensin II (ANG II) levels were increased (68 +/- 12 vs. 20 +/- 5 pg/g, P < 0.01) as steady-state ANG II type 1 (AT(1)) receptor mRNA was decreased 40% and endothelial nitric oxide synthase mRNA levels were increased 2.5-fold in PO versus control dogs (P < 0.05). Total ANG II receptor binding sites of freshly prepared cardiac membranes demonstrated no difference in the dissociation constant, but there was a 60% decrease in maximum binding (B(max)) in PO versus control dogs (P < 0.01). LV ANG II levels correlated negatively with AT(1) receptor mRNA levels (r = -0.75, P < 0.01) and total AT(1) receptor B(max) (r = -0.77, P < 0.02). These results suggest that LV ANG II negatively regulates AT(1) receptor expression and that this is an adaptive response to chronic PO before the onset of myocardial failure in the young dog.
Authors:
David Schultz; Xuefeng Su; Chih-Chang Wei; Sanford P Bishop; Pamela Powell; Gerald H Hankes; A Ray Dillon; Patricia Rynders; Francis G Spinale; Gregory Walcott; Raymond Ideker; Louis J Dell'Italia
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  282     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-01-14     Completed Date:  2002-02-14     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H749-56     Citation Subset:  IM    
Affiliation:
Emory University, Atlanta, Georgia 30322, USA.
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological / physiology
Age Factors
Angiotensin II / metabolism
Animals
Aorta
Arrhythmias, Cardiac / metabolism,  pathology,  physiopathology
Blood Pressure / physiology
Cardiac Volume / physiology
Cardiomegaly / metabolism*,  pathology,  physiopathology
Disease Models, Animal
Dogs
Down-Regulation / physiology
Electrophysiology
Gene Expression / physiology
Muscle Fibers, Skeletal / physiology
Myocardium / metabolism*,  pathology
RNA, Messenger / analysis
Receptor, Angiotensin, Type 1
Receptors, Angiotensin / genetics*,  metabolism*
Renin-Angiotensin System / physiology
Ventricular Function, Left / physiology
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/Receptor, Angiotensin, Type 1; 0/Receptors, Angiotensin; 11128-99-7/Angiotensin II

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