IMPAIRED DIASTOLIC FUNCTION AND CORONARY RESERVE IN GENETIC-HYPERTENSION - ROLE OF INTERSTITIAL FIBROSIS AND MEDIAL THICKENING OF INTRAMYOCARDIAL CORONARY-ARTERIES
IMPAIRED DIASTOLIC FUNCTION AND CORONARY RESERVE IN GENETIC-HYPERTENSION - ROLE OF INTERSTITIAL FIBROSIS AND MEDIAL THICKENING OF INTRAMYOCARDIAL CORONARY-ARTERIES
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DOI：
10.1161/01.res.69.1.107
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发表时间：
1991-07-01
影响因子：
20.1
通讯作者：
WEBER, KT
中科院分区：
文献类型：
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作者：
BRILLA, CG;JANICKI, JS;WEBER, KT
遗传性高血压大鼠左室肥厚（LVH）伴随着异常的心肌舒张刚度和受损的冠状动脉储备。 这些功能缺陷是否与心肌的结构重塑有关，包括间质和血管周围纤维化、肌细胞肥大和心肌内冠状动脉中膜增厚，尚不确定。 为了解决这些问题，14周龄的雄性自发性高血压大鼠，建立高血压和左心室肥厚的低剂量（SLO组：2.5 mg/kg/天，n = 11）或高剂量（SHI组：20 mg/kg/天，n = 9）口服赖诺普利12周，以维持高血压和左心室肥厚或正常化动脉压和心肌质量，分别。 当SHI和SLO组与年龄和性别匹配的26周龄未经治疗的自发性高血压大鼠（n = 11）和血压正常的Wistar-Kyoto大鼠（n = 9）进行比较时，我们发现：1）血压正常化（p < 0.005）和LVH完全消退（p < 0.005），而在SLO组中没有显著的血压或LVH降低，2）SHI和SLO组中形态测定的心肌间质和血管周围纤维化完全消退（p < 0.025）与离体心脏舒张期僵硬度正常化相关（p < 0.025），3）仅SHI组心肌内冠状动脉的中壁增厚消退（p < 0.005），伴随着冠状动脉血管舒张储备对腺苷的正常化（p < 0.005）。 因此，间质纤维化而不是LVH是导致异常心肌舒张僵硬的原因，而受动脉压影响的心肌内阻力血管的中壁增厚与冠状动脉储备受损相关。
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.