Estrogen replacement increases coronary artery distensibility in ovariectomized rats

1999 ◽  
Vol 77 (1) ◽  
pp. 75-78 ◽  
Author(s):  
Yunlong Zhang ◽  
Sandra T Davidge
Keyword(s):  
Wall Thickness ◽  
Vascular Remodeling ◽  
Mesenteric Arteries ◽  
Ovariectomized Rats ◽  
Estrogen Replacement ◽  
Sprague Dawley ◽  
Dual Chamber ◽  
Arterial Distensibility ◽  
Sprague Dawley Rats ◽  
17Β Estradiol

The effect of estrogen on the passive characteristics of arteries is not known. We hypothesized that estrogen would increase arterial distensibility as part of its protective effect on the vasculature. Female Sprague-Dawley rats were ovariectomized at 11 weeks of age. One group received a placebo (n = 6), while two other groups (n = 5 each) of rats received a 17β-estradiol pellet (0.15 mg or 0.5 mg with 60-day release). After 4 weeks of estrogen replacement, coronary and mesenteric arteries (<200 µm diameter) were dissected and mounted on a dual-chamber arteriograph. Lumen diameter and wall thickness were measured in pressurized arteries. The relative changes in diameter (distensibility) as well as wall thickness per unit change in pressure were significantly increased (p < 0.05) in the coronary arteries of the 0.5 mg estradiol replaced rats compared with the ovariectomized control animals and the 0.15 mg estradiol replaced rats. Surprisingly, in the mesenteric arteries from the same animals, there was no difference in distensibility or pressure - wall thickness among the groups. This study provides experimental data of a novel hypothesis that estrogen may afford part of its protection through vascular remodeling of the coronary circulation.Key words: vasculature, remodeling, cardiovascular disease.

Effect of the ovarian hormones on GLUT4 expression and contraction-stimulated glucose uptake

2002 ◽  
Vol 282 (5) ◽  
pp. E1139-E1146 ◽  
Author(s):  
S. E. Campbell ◽  
M. A. Febbraio
Keyword(s):  
Glucose Uptake ◽  
Glycogen Content ◽  
Ovariectomized Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Transporter Protein ◽  
Glut4 Expression ◽  
Sprague Dawley Rats ◽  
17Β Estradiol

This study examined the roles of the female sex steroids, 17β-estradiol (E2) and progesterone (Prog), on glucose uptake and GLUT4 protein expression. Female Sprague-Dawley rats were either sham operated (C) or ovariectomized and treated with placebo (O), E2 (E), Prog (P), or both hormones at physiological doses (P + E) or the same dose of Prog with a high dose of E2 (P + HiE) via timed-release pellets inserted at the time of surgery, 15 days before metabolic testing. On the morning of day 15, animals received a 300-μCi injection (ip) of 2-deoxy-[14C]glucose and then either exercised on a motorized treadmill for 30 min at 0.35 m/s or remained sedentary in their cages for the same period. Basal glucose uptake was not different between the treatment groups in either the red or white quadriceps. However, glucose uptake was decreased ( P < 0.05) in O, P, and P + E rats during exercise in the red quadriceps compared with C rats, whereas E and P + HiE treatment restored glucose uptake. Glycogen content in skeletal muscle followed similar trends, with no differences seen in resting animals. Postexercise red quadriceps glycogen levels were higher ( P < 0.05) in the E and P + HiE rats compared with O and P. Treatment of ovariectomized rats with progesterone (P rats) decreased ( P < 0.05) GLUT4 content in the red quadriceps by 21% compared with C rats. These data demonstrate that estrogen-deficient animals have a decreased ability for contraction-stimulated glucose uptake and increased glycogen use during aerobic exercise. However, changes in contraction-stimulated glucose uptake could not be explained by altered transporter protein content, since the absence of E2 had no effect on GLUT4 protein.

Effect of ovarian hormones on mitochondrial enzyme activity in the fat oxidation pathway of skeletal muscle

2001 ◽  
Vol 281 (4) ◽  
pp. E803-E808 ◽  
Author(s):  
S. E. Campbell ◽  
M. A. Febbraio
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Maximal Activity ◽  
Ovariectomized Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Muscle Enzyme ◽  
Sprague Dawley Rats ◽  
Oxidative Pathway ◽  
17Β Estradiol

To examine the roles of 17β-estradiol (E2) and progesterone (Prog) in lipid metabolism, skeletal muscle enzyme activities were studied in female Sprague-Dawley rats. Groups included sham-operated rats (C) and ovariectomized rats treated with placebo (O), E2 (E), Prog (P), both hormones at physiological doses (P + E), or both hormones with a high dose of E2 (P + HiE). Hormone (or vehicle only) delivery was via time-release pellets inserted at the time of surgery, 15 days before metabolic testing. Results demonstrated that carnitine palmitoyltransferase maximal activity was 19, 21, and 19% lower ( P < 0.01) in O, P, and P + E rats, respectively, compared with C rats. Conversely, activity in E and P + HiE rats was 14 and 19% higher ( P < 0.01) than in C. β-Hydroxyacyl-CoA dehydrogenase (β-HAD) maximal activity was 20% lower ( P < 0.01) in O than in C rats; similarly, P and P + E rats were 18 and 19% lower, respectively ( P < 0.01); however, treatment with E2returned β-HAD activity to C levels. These results suggest that E2 plays a role in lipid metabolism by increasing the maximal activity of key enzymes in the fat oxidative pathway of skeletal muscle.

A comparison of ovariectomy models for estrogen studies

2001 ◽  
Vol 280 (3) ◽  
pp. R904-R907 ◽  
Author(s):  
Sandra T. Davidge ◽  
Yunlong Zhang ◽  
Ken G. Stewart
Keyword(s):  
Body Weight ◽  
Vascular Function ◽  
Mesenteric Arteries ◽  
The Other ◽  
Confounding Factors ◽  
Estrogen Replacement ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
And Control ◽  
Estradiol Levels

Many estrogen-replacement studies use ovariectomized animals as controls. However, ovariectomy greatly increases body weight and can enhance the peripheral synthesis of estrogen. Tamoxifen is commonly used as an antiestrogen, but it may elicit mixed agonist or antagonist actions. The aim of our study was to compare vascular function in mesenteric arteries among groups of rats with low estradiol levels. The groups ( n = 5, each) of Sprague-Dawley rats were cycling (diestrus), ovariectomized (OVX), OVX + tamoxifen (OVX-T), OVX + 4-hydroxyandrostene-3,17-dione, an aromatase inhibitor (OVX-A) to prevent peripheral synthesis of estrogen, and control-fed OVX to prevent excess weight gain. Body weight was significantly elevated in only the non-control-fed OVX group. Estrogen levels were significantly greater in the cycling rats compared with the other groups, whereas uterine weights were significantly reduced in only the OVX-A and control-fed OVX groups. Methacholine relaxation was blunted only in the OVX-A and control-fed OVX groups, suggesting a possible estrogenic influence in the non-control-fed OVX and OVX-T groups. These data indicate the potential for confounding factors to decrease the efficacy of OVX controls.

scholarly journals Effects of ovariectomy and estrogen on ischemia-reperfusion injury in hindlimbs of female rats

2001 ◽  
Vol 91 (4) ◽  
pp. 1828-1835 ◽  
Author(s):  
Nicole Stupka ◽  
Peter M. Tiidus
Keyword(s):  
Muscle Damage ◽  
Ischemia Reperfusion Injury ◽  
Serum Insulin ◽  
Ischemia Reperfusion ◽  
Neutrophil Infiltration ◽  
Female Rats ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
17Β Estradiol

The effects of estrogen and ovariectomy on indexes of muscle damage after 2 h of complete hindlimb ischemia and 2 h of reperfusion were investigated in female Sprague-Dawley rats. The rats were assigned to one of three experimental groups: ovariectomized with a 17β-estradiol pellet implant (OE), ovariectomized with a placebo pellet implant (OP), or control with intact ovaries (R). It was hypothesized that following ischemia-reperfusion (I/R), muscle damage indexes [serum creatine kinase (CK) activity, calpain-like activity, inflammatory cell infiltration, and markers of lipid peroxidation (thiobarbituric-reactive substances)] would be lower in the OE and R rats compared with the OP rats due to the protective effects of estrogen. Serum CK activity following I/R was greater ( P < 0.01) in the R rats vs. OP rats and similar in the OP and OE rats. Calpain-like activity was greatest in the R rats ( P < 0.01) and similar in the OP and OE rats. Neutrophil infiltration was assessed using the myeloperoxidase (MPO) assay and immunohistochemical staining for CD43-positive (CD43+) cells. MPO activity was lower ( P < 0.05) in the OE rats compared with any other group and similar in the OP and R rats. The number of CD43+ cells was greater ( P < 0.01) in the OP rats compared with the OE and R rats and similar in the OE and R rats. The OE rats had lower ( P < 0.05) thiobarbituric-reactive substance content following I/R compared with the R and OP rats. Indexes of muscle damage were consistently attenuated in the OE rats but not in the R rats. A 10-fold difference in serum estrogen content may mediate this. Surprisingly, serum CK activity and muscle calpain-like activity were lower ( P< 0.05) in the OP rats compared with the R rats. Increases in serum insulin-like growth factor-1 content ( P < 0.05) due to ovariectomy were hypothesized to account for this finding. Thus both ovariectomy and estrogen supplementation have differential effects on indexes of I/R muscle damage.

Abstract 637: Hydrogen Sulfide Acts on Endothelial Cells to Elicit Dilation.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Nancy L Kanagy ◽  
Jessica M Osmond ◽  
Olan Jackson-Weaver ◽  
Benjimen R Walker
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Hydrogen Sulfide ◽  
Mesenteric Arteries ◽  
Direct Effects ◽  
Sprague Dawley ◽  
Imaging Studies ◽  
Knock Out ◽  
Event Frequency ◽  
Sprague Dawley Rats

Hydrogen sulfide (H 2 S), produced by the enzyme cystathionine-γ lyase (CSE), dilates arteries by hyperpolarizing and relaxing vascular smooth muscle cells (VSMC) and CSE knock-out causes hypertension and endothelial dysfunction showing the importance of this system. However, it is not clear if H 2 S-induced VSMC depolarization and relaxation is mediated by direct effects on VSMC or indirectly through actions on endothelial cells (EC). We reported previously that disrupting EC prevents H 2 S-induced vasodilation suggesting H 2 S might act directly on EC. Because inhibiting large-conductance Ca 2+ -activated K + (BK Ca ) channels also inhibits H 2 S-induced dilation, we hypothesized that H 2 S activates EC BK Ca channels to hyperpolarize EC and increase EC Ca 2+ which stimulates release of a secondary hyperpolarizing factor. Small mesenteric arteries from male Sprague-Dawley rats were used for all experiments. We found that EC disruption prevented H 2 S-induced VSMC membrane potential ( E m ) hyperpolarization. Blocking EC BK Ca channels with luminal application of the BK Ca inhibitor, iberiotoxin (IbTx, 100 nM), also prevented NaHS-induced dilation and VSMC hyperpolarization but did not affect resting VSMC E m showing EC specific actions. Sharp electrode recordings in arteries cut open to expose EC demonstrated H 2 S-induced hyperpolarization of EC while Ca 2+ imaging studies in fluor-4 loaded EC showed that H 2 S increases EC Ca 2+ event frequency. Thus H 2 S can act directly on EC. Inhibiting the EC enzyme cytochrome P 450 2C (Cyp2C) with sulfaphenazole also prevented VSMC depolarization and vasodilation. Finally, inhibiting TRPV4 channels to block the target of the Cyp2C product 11,12-EET inhibited NaHS-induced dilation. Combined with our previous report that CSE inhibition decreases BK Ca currents in EC, these results suggest that H 2 S stimulates EC BK Ca channels and activates Cyp2C upstream of VSMC hyperpolarization and vasodilation.

scholarly journals 2251

2017 ◽  
Vol 1 (S1) ◽  
pp. 60-60
Author(s):  
Andrea Lee Frump ◽  
Margie Albrecht ◽  
Sandra Breuils-Bonnet ◽  
Bakhtiyor Yakubov ◽  
Mary Beth Brown ◽  
...  
Keyword(s):  
Western Blot ◽  
Knockout Mice ◽  
Sprague Dawley ◽  
Protein Receptor ◽  
Morphogenetic Protein ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Study Population ◽  
Direct Binding ◽  
17Β Estradiol

OBJECTIVES/SPECIFIC AIMS: Women with pulmonary arterial hypertension (PAH) exhibit superior right ventricular (RV) function and survival compared with men, a phenomenon attributed to poorly understood cardioprotective effects of 17β-estradiol (E2). We hypothesize that E2, through ERα, attenuates PH-induced RV dysfunction by upregulating the pro-contractile and pro-angiogenic peptide apelin. This ERα-mediated increase in apelin is mediated by the myocardial remodeling effector bone morphogenetic protein receptor 2 (BMPR2). METHODS/STUDY POPULATION: ERα, BMPR2, and apelin were measured (western blot) in RVs from patients with PAH-induced RV failure and in RV homogenates from male or female Sprague-Dawley rats with sugen/hypoxia (SuHx) or monocrotaline (MCT)-induced PH. H9c2 rat cardiomyoblasts and cardiac endothelial cells were stressed with TNF-α (10 ng/mL) or staurosporine (50 nM)±E2 (100 nM; 24 h). ERα-, BMPR2-, and apelin-dependence were evaluated by siRNA (5 pM). Downstream apelin target and pro-survival factor ERK1/2 expression was measured (western blot). p<0.05 by ANOVA was considered significant. RESULTS/ANTICIPATED RESULTS: ERα correlated positively with BMPR2 and apelin expression in SuHx-RVs and human RVs. Treatment of SuHx-PH rats with E2 or ERα agonist increased RV BMPR2 and apelin, whereas RV apelin was decreased in E2-treated hypoxic ERα knockout mice (p<0.05), but not in ERβ knockout mice. In H9c2 cells, E2 or ERα agonist attenuated TNF-α- or staurosporine-induced decreases in BMPR2, apelin, and phospho-ERK1/2 (p<0.05 for all endpoints). E2 protection was lost in presence of siRNA directed against ERα, BMPR2, or apelin (p<0.05). ERα was necessary for E2-mediated increases in BMPR2, apelin, and ERK1/2, and BMPR2 was required for the E2-mediated increase in apelin (p<0.05 for siRNA vs. scramble). ERα, BMPR2, and apelin protein was increased in decompensated human RVs but downstream phospho-ERK signaling was disrupted. DISCUSSION/SIGNIFICANCE OF IMPACT: E2, via ERα, increases BMPR2 and apelin in the failing RV and in stressed rat cardiomyoblasts. The E2-mediated increase in apelin is BMPR2-dependent and likely occurs through direct binding of ERα to the BMPR2 promoter. Harnessing this E2-ERα-BMPR2-apelin axis during RV compensation may lead to novel, RV-targeted therapies for PAH patients of either sex.

17β-Estradiol modulates vasoconstriction induced by endothelin-1 following trauma-hemorrhage

2007 ◽  
Vol 292 (1) ◽  
pp. H245-H250 ◽  
Author(s):  
Zheng F. Ba ◽  
Ailing Lu ◽  
Tomoharu Shimizu ◽  
László Szalay ◽  
Martin G. Schwacha ◽  
...  
Keyword(s):  
Control Level ◽  
No Synthase ◽  
Sprague Dawley ◽  
Response Curves ◽  
Endothelin 1 ◽  
Sprague Dawley Rats ◽  
17Β Estradiol ◽  
Synthase Inhibitor

Although endothelin-1 (ET-1) induces vasoconstriction, it remains unknown whether 17β-estradiol (E2) treatment following trauma-hemorrhage alters these ET-1-induced vasoconstrictive effects. In addition, the role of the specific estrogen receptor (ER) subtypes (ER-α and ER-β) and the endothelium-localized downstream mechanisms of actions of E2 remain unclear. We hypothesized that E2 attenuates increased ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway. To study this, aortic rings were isolated from male Sprague-Dawley rats following trauma-hemorrhage with or without E2 treatment, and alterations in tension were determined in vitro. Dose-response curves to ET-1 were determined, and the vasoactive properties of E2, propylpyrazole triol (PPT, ER-α agonist), and diarylpropionitrile (DPN, ER-β agonist) were determined. The results showed that trauma-hemorrhage significantly increased ET-1-induced vasoconstriction; however, administration of E2 normalized ET-1-induced vasoconstriction in trauma-hemorrhage vessels to the sham-operated control level. The ER-β agonist DPN counteracted ET-1-induced vasoconstriction, whereas the ER-α agonist PPT was ineffective. Moreover, the vasorelaxing effects of E2 were not observed in endothelium-denuded aortic rings or by pretreatment of the rings with a nitric oxide (NO) synthase inhibitor. Cyclooxygenase inhibition with indomethacin had no effect on the action of E2. Thus, E2 administration attenuates ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway that is dependent on endothelium-derived NO synthesis.

EFFECTS OF SIMVASTATIN ON FEMORAL BIOMECHANICS IN OVARIECTOMIZED RATS

2013 ◽  
Vol 13 (02) ◽  
pp. 1350048
Author(s):  
XIAOCHONG JIAN ◽  
JIANG CHEN ◽  
LINLIN ZHANG ◽  
FUHUA YAN ◽  
YANJUN ZENG
Keyword(s):  
Bending Test ◽  
Ovariectomized Rats ◽  
Sprague Dawley ◽  
Simvastatin Treatment ◽  
Three Point Bending ◽  
Sprague Dawley Rats ◽  
Biomechanical Parameters ◽  
Inorganic Constituents ◽  
Time Of Administration ◽  
Maximal Strain

Objective: To investigate the effect of simvastatin on the biomechanical characteristics of the femur in ovariectomized rats. Material and methods: Fifty-four female Sprague-Dawley rats, aged three months old, were randomly divided into three groups: sham-operated group ( SHAM; n = 18), ovariectomized group (OVX; n = 18), and ovariectomized with simvastatin treatment group (OVX+SIM; n = 18). Eight weeks after being ovariectomized, simvastatin was administered orally at 5 mg/kg each day in the OVX + SIM group. The animals were sacrificed at either four or 12 weeks after administration and femurs were obtained. Biomechanical parameters were measured by the three-point bending test. Results: There were no significant differences in the maximal strain and flexibility strain between the OVX and OVX + SIM groups at either four or 12 weeks after administration (p > 0.05). In contrast, significant differences in flexibility loading at four weeks and in maximal loading, flexibility loading, and the coefficient of bending ductility between the OVX and OVX + SIM groups at either four or 12 weeks (p < 0.05 and p < 0.01, respectively). Intergroup comparisons showed that maximal loading and flexibility loading have significant differences in the OVX + SIM group (p < 0.01). Conclusion: Simvastatin shows potential in promoting bone remodeling, changing bone micro-architecture, and influencing the integration and distribution ratio of organic and inorganic constituents in bone tissue of ovariectomized rats. In addition, a longer time of administration with simvastatin could enhance the femoral strength.

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