Angiotension AT1Receptor Inhibition in Pacing Induced Heart Failure: Effects on Left Ventricular Myocardial Collagen Content and Composition

The progression of left ventricular (LV) dilation with congestive heart failure (CHF) is associated with an increased incidence of morbidity and mortality. The LV myocardial extracellular matrix has been implicated to play an important role in maintaining chamber shape and myocyte alignment. While a...

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Bibliographic Details
Published in:Journal of molecular and cellular cardiology 1998-11, Vol.30 (11), p.2355-2364
Main Authors: Clair, Mark J., Krombach, R.Stephen, Coker, Mysti L., Heslin, Terri L., Kribbs, Scott B., de Gasparo, Marc, Spinale, Francis G.
Format: Article
Language:English
Subjects:
Fractional shortening
myocardial collagen, myocardial hydroxyproline
pig
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Summary:The progression of left ventricular (LV) dilation with congestive heart failure (CHF) is associated with an increased incidence of morbidity and mortality. The LV myocardial extracellular matrix has been implicated to play an important role in maintaining chamber shape and myocyte alignment. While angiotensin II AT1receptor (Ang AT1) receptor activation has been demonstrated to contribute to increased vascular resistance with the CHF, whether activation of the myocardial Ang AT1receptor system contributes to LV dilation and myocardial collagen remodelling with CHF remains unclear. The goal of this study was to examine the effects of Ang AT1receptor inhibition on LV geometry and myocardial collagen content and structure with the development of pacing CHF. Pigs (25 kg) were instrumented in order to measure LV function in the conscious state and were assigned to one of three groups: (1) Pacing CHF: rapid atrial pacing (240 bpm) for 3 weeks (n=7); (2) Pacing CHF and Ang AT1Block: concomitant Ang AT1receptor blockade (valsartan, Novartis, Basel 60 mg/day) and rapid pacing (n=7); (3) sham controls (n=7). The Ang AT1receptor antagonist was delivered by osmotic minipump and this dose has been demonstrated previously to significantly blunt the Ang-II pressor response. LV pump function and geometry was assessed by echocardiography and LV myocardial collagen content by computer assisted histomorphometry and biochemistry. In the pacing CHF group, LV fractional shortening was reduced (17±2v45±1%) and LV end-diastolic dimension increased (5.91±0.09v3.75±0.07 cm) compared to controls (P
ISSN:0022-2828
1095-8584
DOI:10.1006/jmcc.1998.0796