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

C. G. Brilla, J. S. Janicki, Karl Weber

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Abstract

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 μg/min) were eamined 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<0.025; WKY, 2.8±0.5%), 3) normalization of myocardial stiffness constant from 19.5±0.9 to 13.7±1.3 (p<0.0025; 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<0.025; WKY, 0.6±0.1) and medial thickening from 12.3±0.6 to 7.4±0.5 μm (p<0.005; WKY, 7.4±0.4 μm), and 4) a restoration of coronary vasodilator response to adenosine from 12.3±0.9 to 26.0±1.4 ml/min/g (p<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 vascualr reserve to normal. Conclusions. These cardioreparative properties of angiotensin converting enzyme inhibition may be valuable in reversing left ventricular dysfunction in hypertensive heart disease.

Original languageEnglish (US)
Pages (from-to)1771-1779
Number of pages9
JournalCirculation
Volume83
Issue number5
DOIs
StatePublished - Jan 1 1991
Externally publishedYes

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Lisinopril
Left Ventricular Hypertrophy
Hypertension
Coronary Vessels
Peptidyl-Dipeptidase A
Adenosine
Fibrosis
Collagen
Fibrillar Collagens
Ventricular Dysfunction
Adventitia
Vascular Stiffness
Left Ventricular Dysfunction
Vasodilator Agents
Hypertrophy
Heart Diseases
Myocardium
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Cardioreparative effects of lisinopril in rats with genetic hypertension and left ventricular hypertrophy. / Brilla, C. G.; Janicki, J. S.; Weber, Karl.

In: Circulation, Vol. 83, No. 5, 01.01.1991, p. 1771-1779.

Research output: Contribution to journalArticle

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N2 - 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 μg/min) were eamined 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<0.025; WKY, 2.8±0.5%), 3) normalization of myocardial stiffness constant from 19.5±0.9 to 13.7±1.3 (p<0.0025; 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<0.025; WKY, 0.6±0.1) and medial thickening from 12.3±0.6 to 7.4±0.5 μm (p<0.005; WKY, 7.4±0.4 μm), and 4) a restoration of coronary vasodilator response to adenosine from 12.3±0.9 to 26.0±1.4 ml/min/g (p<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 vascualr reserve to normal. Conclusions. These cardioreparative properties of angiotensin converting enzyme inhibition may be valuable in reversing left ventricular dysfunction in hypertensive heart disease.

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