© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Myocardial stiffness is determined by ventricular fibrosis, but not by compensatory or excessive hypertrophy in hypertensive heart
aDepartment of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Japan
bGenome Information Research Center, Osaka University, Suita, Japan
cDepartment of Cardiovascular Sciences, Tokyo Women's Medical University, Tokyo, Japan
dDepartment of Biochemistry, Hyogo College of Medicine, Nishinomiya, Japan
masuyama{at}medone.med.osaka-u.ac.jp
* Corresponding author. Tel.: +81-6-6879-6612; fax: +81-6-6879-6613
Objectives: Diastolic dysfunction that determines symptoms and prognosis in patients with systolic dysfunction causes heart failure even in the absence of systolic dysfunction. Our recent studies have suggested that myocardial stiffening is likely to play a crucial role in triggering deleterious cardiac disorder. This study investigated differential contribution of left ventricular (LV) hypertrophy and fibrosis to myocardial stiffening in the pressure-overloaded heart. Methods: Dahl-Iwai salt-sensitive rats fed on high-salt diet since 7 weeks transit to congestive heart failure at 20 weeks following development of hypertension, LV hypertrophy and fibrosis, and 20 such rats were divided into three groups: rats treated with angiotensin II type 1 receptor antagonist from 8 weeks (n = 7), rats treated with calcineurin inhibitor from 8 weeks (n = 6), and untreated rats (n = 7). Results: Administration of angiotensin II type 1 receptor antagonist and calcineurin inhibitor did not affect blood pressure and allowed the development of compensatory hypertrophy. However, in contrast to the untreated rats, additive and excessive LV hypertrophy was not observed in either of the treated rats. The blockade of angiotensin II kept LV hydroxyproline content, a ratio of type I to type III collagen mRNA levels, collagen solubility and myocardial stiffness constant at the normal level; however, the calcineurin inhibition failed. Conclusions: Myocardial stiffening may be attributed to progressive collagen accumulation, collagen phenotype shift and enhanced collagen cross-linking, but not to either compensatory LV hypertrophy or LV hypertrophy that progresses from the compensatory stage.
KEYWORDS Fibrosis; Heart failure; Hypertension; Ventricular function
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