Temporal characteristics of cardiomyocyte hypertrophy in the spontaneously hypertensive rat.
BACKGROUND
The spontaneously hypertensive rat (SHR) is frequently used as model of cardiovascular disease, with considerable disparity in reported parameters of hypertrophy. The aim of this study was to assess the temporal changes occurring during the development and progression of cardiomyocyte hypertrophy in SHR, subsequent to pressure overload, compared to changes associated with normal aging using the normotensive Wistar-Kyoto (WKY) rat.


METHODS
Ventricular cardiomyocytes were isolated from rats at 8, 12, 16, 20 and 24 weeks, and parameters of hypertrophy (cell dimensions, protein mass, de novo protein synthesis, and gene expression) and function (contraction and hypertrophic responsiveness in vitro) were assessed.


RESULTS
Hypertension was evident at > or =7 weeks in SHRs. Heart:body mass ratio, cardiomyocyte protein mass and width were elevated (P<.05) in SHRs at 16-20 weeks compared to WKYs. In SHRs compared to WKYs at 16 weeks, there was a transient increase (P<.05) in protein synthesis, enhanced hypertrophic responsiveness to phorbol-12-myristate-13-acetate, and induced hypertrophic responsiveness to isoprenaline. Skeletal-alpha-actin mRNA was detected in SHR but not WKY cells at all ages. ANP mRNA was lower in SHR than in WKY cells at 8-20, but progressively increased (P<.05) from 12 to 24 weeks within SHRs. Contractile function increased (P<.05) at 20 weeks in SHR compared to WKY rats.


CONCLUSIONS
Structural and functional changes occurring at the cellular level in the myocardium of SHR follow a distinct pattern, such that pressure overload was initially accompanied by expressional changes (8-12 weeks), followed by active hypertrophic growth and enhanced function (16-20 weeks), which subsequently decelerated as stable compensation was attained.
Bell
David
D
Department of Therapeutics and Pharmacology, Centre for Cardiovascular and Genetics Research, School of Medicine, Queen's University Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK. d.bell@qub.ac.uk
Kelso
Elizabeth J
EJ
Argent
Cymone C H
CC
Lee
Graham R
GR
Allen
Adrian R
AR
McDermott
Barbara J
BJ
D000199:Actins / Q000378:metabolism; D000375:Aging; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006973:Hypertension / Q000473:pathology* / Q000503:physiopathology; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000199:Actins; D009320:Atrial Natriuretic Factor