Temporal regression of myocyte hypertrophy in hypertensive, heart failure-prone rats treated with an AT1-receptor antagonist.
BACKGROUND
A recent study showed reverse remodeling of left ventricular myocyte shape when the type 1 angiotensin II (AT1)-receptor antagonist L-158,809 was administered to spontaneously hypertensive heart failure (SHHF) rats 4 months before the onset of failure. The aim of this study was to characterize temporally early treatment-induced reverse remodeling at the organ and cellular level by echocardiography and morphometry of isolated left ventricular myocytes.


RESULTS
L-158,809 was administered to 9-month-old SHHF rats. Blood pressure normalized shortly after initiation of treatment. Isolated myocytes were collected in terminal experiments to assess cell remodeling. L-158,809 reduced myocyte volume and cross-sectional area significantly after 1 week of treatment with maximal regression of hypertrophy, including reduced cell length, obtained by 4 weeks. Reduced wall thickness was clearly detectable by echocardiography within 4 weeks after initiation of treatment.


CONCLUSIONS
Regression of left ventricular myocyte hypertrophy occurred rapidly after initiation of AT1-blocker therapy in SHHF rats and was completed within 1 month. Regression of myocyte hypertrophy was associated with reduced wall thickness, which was detected consistently by echocardiography within 1 month after initiation of treatment.
Tamura
Tetsutaro
T
South Dakota Health Research Foundation-Cardiovascular Research Institute, Sioux Falls, SD 57105-1570, USA.
Said
Suleman
S
Andersen
Susan M K
SM
McCune
Sylvia A
SA
Mochizuki
Seibu
S
Gerdes
A Martin
AM
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D005260:Female; D006973:Hypertension / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000473:pathology; D007093:Imidazoles / Q000627:therapeutic use*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D013777:Tetrazoles / Q000627:therapeutic use*; D013997:Time Factors
D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; C070967:L 158809