Impaired diastolic function and coronary reserve in genetic hypertension

Role of interstitial fibrosis and medial thickening of intramyocardial coronary arteries

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

Research output: Contribution to journalArticle

383 Citations (Scopus)

Abstract

Left ventricular hypertrophy (LVH) in rats with genetic hypertension is accompanied by abnormal myocardial diastolic stiffness and impaired coronary reserve. Whether these functional defects are related to a structural remodeling of the myocardium that includes an interstitial and perivascular fibrosis, myocyte hypertrophy, and medial thickening of intramyocardial coronary arteries is uncertain. To address these issues, 14-week-old male spontaneously hypertensive rats with established hypertension and LVH were treated with low-dose (SLO group: 2.5 mg/kg/day, n = 11) or high-dose (SHI group: 20 mg/kg/day, n = 9) oral lisinopril for 12 weeks to sustain hypertension and LVH or to normalize arterial pressure and myocardial mass, respectively. When SHI and SLO groups were compared with age- and sex-matched 26-week-old untreated spontaneously hypertensive rats (n = 11) and normotensive Wistar-Kyoto rats (n = 9), we found 1) normalization of blood pressure (p < 0.005) and complete regression of LVH (p < 0.005) in the SHI group and no significant blood pressure or LVH reduction in the SLO group, 2) complete regression of morphometrically determined myocardial interstitial and perivascular fibrosis in SHI and SLO groups (p < 0.025) associated with normalization of diastolic stiffness, measured in the isolated heart (p < 0.025), and 3) regression of medial wall thickening of intramyocardial coronary arteries only in the SHI group (p < 0.005), accompanied by a normalization of coronary vasodilator reserve to adenosine (p < 0.005). Thus, interstitial fibrosis and not LVH is responsible for abnormal myocardial diastolic stiffness, whereas medial wall thickening of intramyocardial resistance vessels, influenced by arterial pressure, is associated with impaired coronary reserve.

Original languageEnglish (US)
Pages (from-to)107-115
Number of pages9
JournalCirculation research
Volume69
Issue number1
DOIs
StatePublished - Jan 1 1991

Fingerprint

Left Ventricular Hypertrophy
Coronary Vessels
Fibrosis
Hypertension
Inbred SHR Rats
Arterial Pressure
Blood Pressure
Lisinopril
Inbred WKY Rats
Vasodilator Agents
Adenosine
Muscle Cells
Hypertrophy
Myocardium

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

@article{5faef34a8ef64dd2b2a5fabe9c324f4b,
title = "Impaired diastolic function and coronary reserve in genetic hypertension: Role of interstitial fibrosis and medial thickening of intramyocardial coronary arteries",
abstract = "Left ventricular hypertrophy (LVH) in rats with genetic hypertension is accompanied by abnormal myocardial diastolic stiffness and impaired coronary reserve. Whether these functional defects are related to a structural remodeling of the myocardium that includes an interstitial and perivascular fibrosis, myocyte hypertrophy, and medial thickening of intramyocardial coronary arteries is uncertain. To address these issues, 14-week-old male spontaneously hypertensive rats with established hypertension and LVH were treated with low-dose (SLO group: 2.5 mg/kg/day, n = 11) or high-dose (SHI group: 20 mg/kg/day, n = 9) oral lisinopril for 12 weeks to sustain hypertension and LVH or to normalize arterial pressure and myocardial mass, respectively. When SHI and SLO groups were compared with age- and sex-matched 26-week-old untreated spontaneously hypertensive rats (n = 11) and normotensive Wistar-Kyoto rats (n = 9), we found 1) normalization of blood pressure (p < 0.005) and complete regression of LVH (p < 0.005) in the SHI group and no significant blood pressure or LVH reduction in the SLO group, 2) complete regression of morphometrically determined myocardial interstitial and perivascular fibrosis in SHI and SLO groups (p < 0.025) associated with normalization of diastolic stiffness, measured in the isolated heart (p < 0.025), and 3) regression of medial wall thickening of intramyocardial coronary arteries only in the SHI group (p < 0.005), accompanied by a normalization of coronary vasodilator reserve to adenosine (p < 0.005). Thus, interstitial fibrosis and not LVH is responsible for abnormal myocardial diastolic stiffness, whereas medial wall thickening of intramyocardial resistance vessels, influenced by arterial pressure, is associated with impaired coronary reserve.",
author = "Brilla, {C. G.} and Janicki, {J. S.} and Karl Weber",
year = "1991",
month = "1",
day = "1",
doi = "10.1161/01.RES.69.1.107",
language = "English (US)",
volume = "69",
pages = "107--115",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Impaired diastolic function and coronary reserve in genetic hypertension

T2 - Role of interstitial fibrosis and medial thickening of intramyocardial coronary arteries

AU - Brilla, C. G.

AU - Janicki, J. S.

AU - Weber, Karl

PY - 1991/1/1

Y1 - 1991/1/1

N2 - Left ventricular hypertrophy (LVH) in rats with genetic hypertension is accompanied by abnormal myocardial diastolic stiffness and impaired coronary reserve. Whether these functional defects are related to a structural remodeling of the myocardium that includes an interstitial and perivascular fibrosis, myocyte hypertrophy, and medial thickening of intramyocardial coronary arteries is uncertain. To address these issues, 14-week-old male spontaneously hypertensive rats with established hypertension and LVH were treated with low-dose (SLO group: 2.5 mg/kg/day, n = 11) or high-dose (SHI group: 20 mg/kg/day, n = 9) oral lisinopril for 12 weeks to sustain hypertension and LVH or to normalize arterial pressure and myocardial mass, respectively. When SHI and SLO groups were compared with age- and sex-matched 26-week-old untreated spontaneously hypertensive rats (n = 11) and normotensive Wistar-Kyoto rats (n = 9), we found 1) normalization of blood pressure (p < 0.005) and complete regression of LVH (p < 0.005) in the SHI group and no significant blood pressure or LVH reduction in the SLO group, 2) complete regression of morphometrically determined myocardial interstitial and perivascular fibrosis in SHI and SLO groups (p < 0.025) associated with normalization of diastolic stiffness, measured in the isolated heart (p < 0.025), and 3) regression of medial wall thickening of intramyocardial coronary arteries only in the SHI group (p < 0.005), accompanied by a normalization of coronary vasodilator reserve to adenosine (p < 0.005). Thus, interstitial fibrosis and not LVH is responsible for abnormal myocardial diastolic stiffness, whereas medial wall thickening of intramyocardial resistance vessels, influenced by arterial pressure, is associated with impaired coronary reserve.

AB - Left ventricular hypertrophy (LVH) in rats with genetic hypertension is accompanied by abnormal myocardial diastolic stiffness and impaired coronary reserve. Whether these functional defects are related to a structural remodeling of the myocardium that includes an interstitial and perivascular fibrosis, myocyte hypertrophy, and medial thickening of intramyocardial coronary arteries is uncertain. To address these issues, 14-week-old male spontaneously hypertensive rats with established hypertension and LVH were treated with low-dose (SLO group: 2.5 mg/kg/day, n = 11) or high-dose (SHI group: 20 mg/kg/day, n = 9) oral lisinopril for 12 weeks to sustain hypertension and LVH or to normalize arterial pressure and myocardial mass, respectively. When SHI and SLO groups were compared with age- and sex-matched 26-week-old untreated spontaneously hypertensive rats (n = 11) and normotensive Wistar-Kyoto rats (n = 9), we found 1) normalization of blood pressure (p < 0.005) and complete regression of LVH (p < 0.005) in the SHI group and no significant blood pressure or LVH reduction in the SLO group, 2) complete regression of morphometrically determined myocardial interstitial and perivascular fibrosis in SHI and SLO groups (p < 0.025) associated with normalization of diastolic stiffness, measured in the isolated heart (p < 0.025), and 3) regression of medial wall thickening of intramyocardial coronary arteries only in the SHI group (p < 0.005), accompanied by a normalization of coronary vasodilator reserve to adenosine (p < 0.005). Thus, interstitial fibrosis and not LVH is responsible for abnormal myocardial diastolic stiffness, whereas medial wall thickening of intramyocardial resistance vessels, influenced by arterial pressure, is associated with impaired coronary reserve.

UR - http://www.scopus.com/inward/record.url?scp=0025826964&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025826964&partnerID=8YFLogxK

U2 - 10.1161/01.RES.69.1.107

DO - 10.1161/01.RES.69.1.107

M3 - Article

VL - 69

SP - 107

EP - 115

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 1

ER -