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Circulation, Vol 83, 1771-1779, Copyright © 1991 by American Heart Association
CG Brilla, JS Janicki and KT Weber
BACKGROUND. In genetic and acquired hypertension, a structural remodeling
of the nonmyocyte compartment of the myocardium, including the accumulation
of fibrillar collagen within the interstitium and adventitia of
intramyocardial coronary arteries and a medial thickening of these vessels,
represents a determinant of pathological hypertrophy that leads to
ventricular dysfunction. METHODS AND RESULTS. To evaluate the benefit of
angiotensin converting enzyme inhibition in reversing this interstitial and
vascular remodeling in the rat with genetic spontaneous hypertension (SHR)
and established left ventricular hypertrophy (LVH), we treated 14-week-old
male SHR with oral lisinopril (average dose, 15 mg/kg/day) for 12 weeks.
Myocardial stiffness and coronary vascular reserve to adenosine (800
micrograms/min) were examined in the isolated heart; myocardial collagen
and intramural coronary artery architecture were analyzed morphometrically.
In lisinopril-treated SHR compared with 14-week-old baseline or 26-week-
old untreated SHR and age- and sex-matched Wistar-Kyoto (WKY) controls, we
found 1) a regression in LVH and normalization of blood pressure, 2) a
complete regression of interstitial fibrosis, represented by a decrease of
interstitial collagen volume fraction from 7.0 +/- 1.3% to 3.2 +/- 0.3% (p
less than 0.025; WKY, 2.8 +/- 0.5%), 3) normalization of myocardial
stiffness constant from 19.5 +/- 0.9 to 13.7 +/- 1.3 (p less than 0.025;
WKY, 13.8 +/- 2.2), 4) a reversal of intramural coronary artery remodeling,
including a decrease in the ratio of perivascular fibrosis to vessel lumen
size from 1.4 +/- 0.2 to 0.4 +/- 0.1 (p less than 0.025; WKY, 0.6 +/- 0.1)
and medial thickening from 12.3 +/- 0.6 to 7.4 +/- 0.5 microns (p less than
0.005; WKY, 7.4 +/- 0.4 microns), and 4) a restoration of coronary
vasodilator response to adenosine from 12.3 +/- 0.9 to 26.0 +/- 1.4
ml/min/g (p less than 0.005; WKY, 21.8 +/- 2.2 ml/min/g). Thus, in SHR with
LVH and adverse structural remodeling of the cardiac interstitium,
lisinopril reversed fibrous tissue accumulation and medial thickening of
intramyocardial coronary arteries and restored myocardial stiffness and
coronary vascular reserve to normal. CONCLUSIONS. These cardioreparative
properties of angiotensin converting enzyme inhibition may be valuable in
reversing left ventricular dysfunction in hypertensive heart disease.
ARTICLES
Cardioreparative effects of lisinopril in rats with genetic hypertension and left ventricular hypertrophy
Cardiovascular Institute, Michael Reese Hospital, University of Chicago Pritzker School of Medicine.
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