INSERM U, Amiens University Medical Center, France.
Am J Physiol Heart Circ Physiol. 2012 Apr 1;302(7):H1524-32. doi: 10.1152/ajpheart.00955.2010. Epub 2012 Jan 27.
Left ventricular (LV) diastolic dysfunction, particularly relaxation abnormalities, are known to be associated with the development of LV hypertrophy (LVH). Preliminary human and animal studies suggested that early LV diastolic dysfunction may be revealed independently of LVH. However, whether LV diastolic dysfunction is compromised before the onset of hypertension and LVH remains unknown. We therefore evaluated LV diastolic function in spontaneously hypertensive rats (SHR) at different ages and tested whether LV diastolic dysfunction is associated with abnormal intracellular calcium homeostasis. LV systolic and diastolic functions were evaluated by invasive and echocardiographic methods in 3-week-old (without hypertension) and 5-week-old (with hypertension) SHR and Wistar-Kyoto control rats. Basal intracytoplasmic calcium and sarcoplasmic reticulum (SR) Ca(2+) contents were measured in cardiomyocytes using fura-2 AM. Sarco(endo)plasmic Ca(2+)-ATPase isoform 2a (SERCA 2a) and phospholamban (PLB) expressions were quantified by Western blot and quantitative RT-PCR techniques. LV relaxation dysfunction was observed in 3-week-old SHR rats before onset of hypertension and LVH. An increase in basal intracytoplasmic Ca(2+) and a decrease in SR Ca(2+) release were demonstrated in SHR. Decreased expression of SERCA 2a and Ser16 PLB (p16-PLB) protein levels was also observed in SHR rats, whereas mRNA expression was not decreased. For the first time, we have shown that LV myocardial dysfunction precedes hypertension in 3-week-old SHR rats. This LV myocardial dysfunction was associated with high diastolic Ca(2+) possibly due to decreased SERCA 2a and p16-PLB protein levels. Diastolic dysfunction may be a potential predictive marker of arterial hypertension in genetic hypertension syndromes.
左心室（LV）舒张功能障碍，特别是舒张功能异常，与 LV 肥厚（LVH）的发展有关。初步的人体和动物研究表明，早期 LV 舒张功能障碍可能在 LVH 之前独立显现。然而，LV 舒张功能障碍是否在高血压和 LVH 之前受损仍不清楚。因此，我们评估了不同年龄的自发性高血压大鼠（SHR）的 LV 舒张功能，并测试了 LV 舒张功能障碍是否与异常的细胞内钙稳态有关。通过侵入性和超声心动图方法评估 3 周龄（无高血压）和 5 周龄（高血压）SHR 和 Wistar-Kyoto 对照大鼠的 LV 收缩和舒张功能。使用 fura-2 AM 测量心肌细胞中的基础细胞内钙和肌浆网（SR）Ca2+含量。通过 Western blot 和定量 RT-PCR 技术定量测定肌浆网 Ca2+-ATPase 同工型 2a（SERCA 2a）和磷蛋白（PLB）的表达。在高血压和 LVH 发生之前，3 周龄 SHR 大鼠出现 LV 舒张功能障碍。在 SHR 中，观察到基础细胞内 Ca2+增加和 SR Ca2+释放减少。在 SHR 大鼠中，还观察到 SERCA 2a 和 Ser16 PLB（p16-PLB）蛋白水平降低，而 mRNA 表达没有降低。我们首次表明，LV 心肌功能障碍在 3 周龄 SHR 大鼠中早于高血压发生。这种 LV 心肌功能障碍与高舒张[Ca2+]（i）有关，可能是由于 SERCA 2a 和 p16-PLB 蛋白水平降低所致。舒张功能障碍可能是遗传性高血压综合征中动脉高血压的潜在预测标志物。
