Cardioreparative effects of lisinopril in rats with genetic hypertension and left ventricular hypertrophy.
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.


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.
Brilla
C G
CG
Cardiovascular Institute, Michael Reese Hospital, University of Chicago Pritzker School of Medicine.
Janicki
J S
JS
Weber
K T
KT
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology; D004548:Elasticity; D004656:Enalapril / Q000031:analogs & derivatives* / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006321:Heart / Q000503:physiopathology; D006973:Hypertension / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D017706:Lisinopril; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013599:Systole; D014666:Vasomotor System / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D003094:Collagen; D017706:Lisinopril