Abstract 383: 17 beta-Estradiol Enhances Mitochondrial Function of Cerebral Arteries From Ovariectomized Female Rats
Previous studies have provided indirect evidence that circulating sex hormones alter the function of the cerebral circulation perhaps via effects on mitochondrial dynamics. However, effects of estrogen on mitochondrial respiration have never been directly examined. We have previously observed a difference in the mitochondrial function of cerebral arteries from male and female rats but the exact mechanisms are not clear.
We tested the hypothesis that mitochondrial respiration in isolated cerebral arteries from ovariectomized (OVX) Sprague Dawley rats treated with a 21 d release, 0.5 mg of 17 β-estradiol pellet (OVX+E) was enhanced compared with arteries from placebo treated OVX rats. The Seahorse Bioscience XFe24 system was used to measure mitochondrial oxygen consumption rate (pM/min/μg protein) in cerebral arteries. Western blot was used to investigate the arterial expression of proteins. Radioimmunoassay was used to measure serum estradiol level.
Treatment with 17 β-estradiol resulted in a higher serum estradiol level (146.9±18.16 pg/ml) and uterus weight (0.15±0.0058 g) in the OVX+E compared with the OVX (14.7±1.2 pg/ml, 0.07±0.003, respectively; p<0.05). The components of mitochondrial respiration in pM/min/μg protein including basal respiration (147±9), ATP production (44±4), proton leak (102±7), and maximal respiration (212±13) were elevated in OVX+E compared with OVX (105±13, 21±4, 50±6, 138±10, respectively; p<0.05). Expression of the mitochondrial DNA encoded Complexes I and III, the nuclear DNA encoded Complexes II, IV, V, and the voltage-dependent anion channel protein were similar in all groups. However, the ratios of phosphorylated endothelial and neuronal nitric oxide (NO) synthase normalized to total protein were significantly (p<0.05) elevated in the OVX+E (1.43±0.06, 1.15±0.2, respectively) compared with OVX group (0.92±0.06, 0.53±0.19, respectively).
Our findings provide direct evidence for sex-specific differences in mitochondrial function on freshly isolated cerebral arteries. Thus, estradiol replacement enhances the efficacy of the oxidative phosphorylation resulting in an increased mitochondrial respiration which is not due to increased mitochondrial protein expression but may be due to enhanced NO.
Author Disclosures: I. Rutkai: None. S. Dutta: None. K.A. Walter: None. P.V. Katakam: None. D.W. Busija: None.
This research has received full or partial funding support from the American Heart Association, Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).
- © 2015 by American Heart Association, Inc.