In rats with genetic hypertension and left ventricular hypertrophy, lisinopril reduced interstitial collagen volume fraction from 7.0% to 3.2% (p<0.025) and reversed intramural coronary remodeling.
Does lisinopril improve myocardial stiffness and reverse interstitial and vascular remodeling in rats with genetic hypertension and LVH?
Lisinopril reverses interstitial fibrosis, medial thickening of intramyocardial coronary arteries, and normalizes myocardial stiffness and coronary vascular reserve in a rat model of genetic hypertension and LVH.
Absolute Event Rate: 3.2% vs 7%
p-value: p=<0.025
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.
Brilla et al. (1991) studied Genetic hypertension and left ventricular hypertrophy. Lisinopril vs. Untreated baseline/age-matched SHR and Wistar-Kyoto controls was evaluated on Interstitial collagen volume fraction (p=<0.025). In rats with genetic hypertension and left ventricular hypertrophy, lisinopril reduced interstitial collagen volume fraction from 7.0% to 3.2% (p<0.025) and reversed intramural coronary remodeling.