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+)](i) 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.