Impaired diastolic function and coronary reserve in genetic hypertension. Role of interstitial fibrosis and medial thickening of intramyocardial coronary arteries.

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 less than 0.005) and complete regression of LVH (p less than 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 less than 0.025) associated with normalization of diastolic stiffness, measured in the isolated heart (p less than 0.025), and 3) regression of medial wall thickening of intramyocardial coronary arteries only in the SHI group (P less than 0.005), accompanied by a normalization of coronary vasodilator reserve to adenosine (p less than 0.005). Thus, interstitial fibrosis and not LVH is responsible for abnormal myocardial diastolic stiffness, whereas medical wall thickening of intramyocardial resistance vessels, influenced by arterial pressure, is associated with impaired coronary reserve.

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