The estrogen receptor-α agonist 16α-LE2 inhibits cardiac hypertrophy and improves hemodynamic function in estrogen-deficient spontaneously hypertensive rats

Abstract

These results support the hypothesis that activation of ERalpha favorably affects cardiac hypertrophy, myocardial contractility, and gene expression in ovariectomized SHR. Further studies are required to determine whether activation ERbeta mediates redundant or divergent effects.

Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats

“…In line with previous observations, E2 efficiently attenuated cardiac hypertrophy in ovariectomized young SHRs, but blood pressure levels were not significantly different among all of the groups of young SHRs. 10,19 These findings indicate that estrogens are able to attenuate cardiac growth also by direct and blood pressure-independent mechanisms, such as cardiac ANP expression and mitogen-activated protein kinase activation, as we and others have reported before. 20 But in contrast to young animals, estrogen substitution failed to attenuate cardiac hypertrophy in aged SHRs.…”

“…1,9 Blood pressure levels were comparable and not different among all 3 of the groups of young rats and among the different groups of senescent SHRs, which is in line with previous findings, including our own. 10,16 Telemetric blood pressure measurements in senescent SHRs were in good agreement with invasive blood pressure levels and again did not reveal a blood pressure-lowering effect of estradiol. In line with previous observations, blood pressure differed, however, between some groups of aged and young SHRs, because systolic and mean blood pressure was higher in intact and in estrogen-treated senescent SHRs compared with young rats receiving hormone substitution.…”

“…29,30 In contrast to previous studies, which failed to detect measurable amounts of ER␣ and ER␤ protein in the mouse heart, several independent studies reported on robust cardiac expression levels of both ER subtypes in rats and humans. 10,31,32 However, cardiac expression levels of ER␣ and ER␤ may not only vary between different species but also among young and senescent SHRs. Therefore, it is interesting to note that cardiac ER␣ expression was significantly lower in sham-operated and ovariectomized aged rats, whereas ER␤ was detected at comparable amounts in the heart of young and senescent rats.…”

“…10 Pressure curves were measured via polyethylene tubing and a microtip manometer (Millar Instruments) calibrated to midchest level. Systolic and diastolic blood pressure measurements were obtained on catheter placement in the thoracic aorta.…”

“…10 Left ventricular samples were homogenized in ice-cold sample buffer containing a protease inhibitor mixture (Roche), centrifuged, and 500 ng of the extract were subjected to SDS-PAGE analysis using a 6% polyacrylamide gel containing 5% glycerol for 18 hours at 4°C before band visualization by silver staining (Silver Stain Plus, Bio Rad). Band intensities for ␣-and ␤-MHC were determined by densitometry using the ScanPack 3.0 software (Biometra).…”