Effects of ovariectomy and 17β‐oestradiol replacement on [Ca²⁺]_i in female rat cardiac myocytes

Abstract

1. The present study investigated the effects of ovariectomy (OVX) and 17beta-oestradiol replacement on [Ca2+]i in rat freshly isolated cardiac myocytes. 2. Myocytes were isolated from the hearts of sham, OVX and OVX + 17beta-oestradiol-replaced female rats by enzymatic digestion with collagenase. Changes in [Ca2+]i in response to varied extracellular [Ca2+] were measured using the Ca2+-sensitive dye fura-2, with the contractile responses of each cell measured as cell shortening. 3. Increasing extracellular [Ca2+] resulted in increased [Ca2+]i in all three groups. Peak [Ca2+]i and the amplitude of the Ca2+ transient were significantly greater (P < 0.01) in cells from OVX animals compared with cells from both sham and 17beta-oestradiol-replaced OVX animals. 4. The time-course of decay of the Ca2+ transient was significantly faster (P < 0.02) in OVX cells compared with both sham and 17beta-oestradiol-replaced cells. In addition, time to 50% relaxation was significantly faster (P < 0.04) and extent of shortening significantly greater (P < 0.01) in OVX cells than in either sham or 17beta-oestradiol cells. 5. These data demonstrate clear differences in peak [Ca2+]i and the amplitude of the Ca2+ transient between OVX female rat cardiac myocytes compared with intact and 17beta-oestradiol-replaced OVX female rat cardiac myocytes. This suggests that oestrogen may play a long-term role in limiting Ca2+ entry into the cardiac myocyte.

Altered Ca2+ handling by ryanodine receptor and Na+-Ca2+ exchange in the heart from ovariectomized rats: role of protein kinase A

“…A recent study from our laboratory (15) has also shown that Ovx for 6 wk significantly increased the left ventricular developed pressure (LVDP) and maximal rate of developed pressure over time (ϮdP/dt max ) in the isolated perfused rat heart and the effects were reversed by female sex hormone replacement. Moreover, the amplitude of the electrically induced intracellular Ca 2ϩ transient (E [Ca 2ϩ ] i ) was also enhanced in the cardiomyocytes following Ovx and the effect was reversed by female sex hormone replacement (5,15). Together with a previous finding of increase in the Ca 2ϩ responsiveness of myofilament activation in the heart of Ovx rats (37) (2,6,31).…”

“…ovariectomy THERE IS INCREASING EVIDENCE that estrogen regulates the cardiac function by direct action on the myocardium. Ovariectomy (Ovx) has been shown to affect the cardiac contractility (5,22,27,28,37). A recent study from our laboratory (15) has also shown that Ovx for 6 wk significantly increased the left ventricular developed pressure (LVDP) and maximal rate of developed pressure over time (ϮdP/dt max ) in the isolated perfused rat heart and the effects were reversed by female sex hormone replacement.…”

“…In the rat ventricular myocyte, SERCA and NCX have been shown to be responsible for removal of Ca 2ϩ by Ͼ90% and ϳ7%, respectively, and are therefore the mechanisms mainly responsible for relaxation (1,2,13). It has been well documented that the expression and activity of L-type Ca 2ϩ channels were increased following Ovx, which were reversed by replacement with estrogen (5,14,15,22). On the other hand, Ovx failed to affect the expression of either Ca 2ϩ -ATPase (SERCA2a) or phospholamban (24).…”

Effects of Estrogen on Cardiovascular Injury in Ovariectomized Female DahlS.Z- Lepr fa /Lepr fa Rats as a New Animal Model of Metabolic Syndrome

“…48 In contrast, estrogen is reported to have antioxidant effects and to exert direct effects on the vessel wall, such as an increase in vascular NO production and modulation of endothelial NO synthase expression. 49 These observations suggest that additional oxidative stress induced by E 2 may play a role in the enhancement of LV diastolic dysfunction by E 2 in Ovx-DS/obese rats.…”

Dietary fish oil is antihypertrophic but does not enhance postischemic myocardial function in female mice

“…Systemic estrogen has also been shown to afford protection against arrhythmogenesis, ischemia-reperfusion injury, and myocardial hypertrophy (22,35,43). Various in vitro studies suggest that the biological actions and cellular targets of omega-3 PUFA and estrogen may be similar, suggesting that omega-3 PUFA may exert a greater effect in females after a period of estrogen withdrawal; albeit a possible convergence of action has not been directly investigated experimentally (7,18,27,33,47).…”