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Biomedical subjects

Ellen W Seely

Publications and source records attributed to Ellen W Seely.

15 recordsLinked to original sources

Relationship between aldosterone and progesterone in the human menstrual cycle.

CONTEXT: Aldosterone levels increase during the luteal phase of the menstrual cycle. Prior studies examining relationships between aldosterone and female sex hormones did not control for sodium balance, a major determinant of aldosterone production. OBJECTIVES: The objectives of this study were 1) to compare aldosterone levels between menstrual phases among cycling women in high- and low-sodium balance; and 2) to examine the relationships between aldosterone and female sex hormones in women and the effects of sex hormones on rat zona glomerulosa (ZG) cell aldosterone production in vitro. SUBJECTS/INTERVENTIONS: Normotensive, premenopausal women were studied in low- and/or high-sodium balance. Urinary aldosterone, basal serum aldosterone, plasma renin activity (PRA), plasma angiotensin II (AngII), and serum aldosterone after AngII infusion were measured. Isolated rat ZG cells were treated with progesterone, estradiol, or both, and aldosterone was measured. RESULTS: In high-sodium balance, urinary aldosterone, basal serum aldosterone, and serum aldosterone response to infused AngII were significantly greater (P < 0.05) in the luteal vs. follicular phase. PRA, AngII, and potassium did not differ. Progesterone directly correlated with urinary aldosterone, basal serum aldosterone, and serum aldosterone response to infused AngII. Estradiol did not significantly correlate with aldosterone. In low-sodium balance, no significant differences in aldosterone levels between phases were found. In vitro, progesterone increased ZG cell aldosterone production (P < 0.01), whereas estradiol had no effect. CONCLUSIONS: In women, urinary and serum aldosterone levels are significantly higher during the luteal phase in high- but not low-sodium balance, whereas PRA and AngII do not differ between phases. Progesterone may directly contribute to increased luteal phase aldosterone production, independent of the renin-angiotensin system.

Adult↗

Low sex hormone-binding globulin is associated with the metabolic syndrome in postmenopausal women.

Although an association between the metabolic syndrome and hyperandrogenism has been suggested in women with polycystic ovarian syndrome, few studies have investigated this relationship in postmenopausal women. We measured estradiol, testosterone, and sex hormone-binding globulin (SHBG) and calculated the free androgen index (FAI) in 212 postmenopausal women not using hormone therapy in the Women's Health Study. A modified definition of the metabolic syndrome (3 or more of the following: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein, elevated blood pressure, and abnormal glucose metabolism) from the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults was used. Women with the metabolic syndrome had higher mean levels of estradiol, testosterone, and FAI values and lower SHBG levels. Higher FAI and lower SHBG were associated with all components of the metabolic syndrome. After adjustment for BMI and other factors, women in the highest tertile of FAI had an odds ratio of 12.6 (95% confidence interval, 3.8-41.6) for the metabolic syndrome, whereas those in the lowest SHBG tertile had an odds ratio of 7.3 (95% confidence interval, 2.7-19.8). When stratified by body mass index, the associations with high FAI and low SHBG remained significant even in women with body mass index less than 26.7 kg/m2. An androgenic hormone profile is associated with both the individual components of the metabolic syndrome and clustering of metabolic abnormalities in postmenopausal women.

Aged↗

Changes in central arterial pressure waveforms during the normal menstrual cycle.

BACKGROUND: Changes in estradiol and progesterone during the human menstrual cycle may impact vascular and cardiac function. Renin-angiotensin-aldosterone system (RAAS) hormones increase during the luteal phase of the menstrual cycle and may antagonize the vascular effects of estradiol. This study was designed to investigate central arterial changes, cardiac function, and RAAS activity in response to gonadal steroid variations during the menstrual cycle. METHODS: We studied 15 women during the follicular and midluteal phases with determination of estradiol, progesterone, hormones of the RAAS, and spot urine sodium and creatinine levels. Central pulsatile hemodynamics was evaluated using calibrated carotid tonometry and central aortic Doppler flow. Systolic ejection period (SEP) and systolic pressure time integral (SPTI) were computed from carotid pressure waveforms. RESULTS: Levels of estradiol, progesterone, and RAAS hormones were higher in the luteal phase. SEP and SPTI were lower during the luteal phase, whereas central and peripheral blood pressures and measures of arterial stiffness were unchanged between the two phases. The urine sodium-to-creatinine ratio was similar at both phases. CONCLUSION: Central arterial stiffness does not differ between the follicular and midluteal phases of the menstrual cycle in healthy women, despite significant changes in estradiol and progesterone levels. Systole was shortened during the midluteal phase. RAAS activation during the luteal phase may be responsible for a lack of the expected estradiol-mediated reduction in arterial stiffness between the two phases of the menstrual cycle. Because load was unchanged, the decrease in SEP and SPTI may represent a direct effect of estrogen, progesterone, or RAAS activation on ventricular function.

Adult↗

Why is orthostatic tolerance lower in women than in men? Renal and cardiovascular responses to simulated microgravity and the role of midodrine.

BACKGROUND: Exposure to microgravity induces cardiovascular deconditioning, manifested by orthostatic intolerance (OI). We assessed the renal, cardioendocrine, and cardiovascular responses of women and men to simulated microgravity to examine the impact of gender on OI. METHODS: Fifteen healthy female and 14 healthy male subjects were given a constant diet for 3 to 5 days, after which they underwent a tilt-stand test (pre-TST) and began 14 to 16 days of head-down tilt bed rest (HDTB), followed by a repeat tilt-stand test (post-TST). Female subjects began HDTB so that the post-TST was at the same time in their menstrual cycle as their pre-TST. Twenty-four-hour urine collections (daily), hormonal measurements, plethysmography, and cardiovascular system identification were performed. RESULTS: The times to presyncope were significantly different for men and women before (p= .005) and after HDTB (p= .001), with all of the women but only 50% of the men experiencing presyncope during the pre-TST (p= .002) and all of the women but only 64% of the men experiencing presyncope during the post-TST. At baseline, the following differences between women and men were observed: women had higher serum aldosterone levels (p = .02), higher parasympathetic responsiveness (p = .01), lower sympathetic responsiveness (p = .05), and lower venous compliance (p = .05). Several parameters changed with HDTB in both men and women. In a double-blinded randomized trial, midodrine (5 mg orally) or placebo given to female subjects 1 hour before post-TST was ineffective in preventing 01. CONCLUSION: In conclusion, the frequency of OI is higher in women than in men and is not modified by midodrine at the dose used. This increased susceptibility is likely secondary to intrinsic basal differences in the activity of volume-mediated parasympathetic and adrenergic systems and in venous tone. Thus, approaches to reduce OI in women are likely to differ from those effective in men.

Adaptation, Physiological↗

Subclinical inflammation and vascular dysfunction in women with previous gestational diabetes mellitus.

CONTEXT: A history of gestational diabetes (GDM) significantly increases the risk of developing type 2 diabetes, an independent risk factor for cardiovascular disease (CVD). It is not known whether nondiabetic women with prior GDM are also at increased risk of CVD. OBJECTIVE: The aim of this study was to compare biochemical and hemodynamic surrogate markers of CVD in nondiabetic women with and without a history of GDM who were at least 1 yr post delivery. DESIGN: This was a single center cross-sectional study. SETTING: The study was performed in an academic referral center. SUBJECTS: Forty-eight premenopausal healthy women with a history of GDM (n = 25) or a history of normal pregnancy (n = 23) were studied in the follicular phase of the menstrual cycle. MAIN OUTCOME MEASURES: The main outcome measures were: 1) inflammatory markers associated with CVD including C-reactive protein, IL-6, and plasminogen activator inhibitor-1; 2) the adipokine adiponectin; and 3) conduit vessel stiffness. RESULTS: When compared to normal controls, women with prior GDM had higher mean levels of C-reactive protein (3.58 +/- 3.86 vs. 0.52 +/- 0.16 mg/liter; P < 0.001), IL-6 (1.81 +/- 1.04 vs. 0.99 +/- 0.52 pg/ml; P = 0.001), plasminogen activator inhibitor-1 (29.6 +/- 17.6 vs. 16.5 +/- 14.0 ng/ml; P = 0.001), and lower levels of adiponectin (8.9 +/- 3.9 vs. 15.9 +/- 7.3 microg/ml; P = 0.001). Women with prior GDM also had significantly (P </= 0.04) increased peripheral vascular resistance (1658 +/- 290 vs. 1462 +/- 340 dyne.sec/cm(5)), decreased stroke volume (65 +/- 13 vs. 75 +/- 14 ml/beat), and decreased cardiac output (70 +/- 12 vs. 74 +/- 13 ml/sec) when compared to controls, after adjusting for body mass index. CONCLUSIONS: Nondiabetic women with prior GDM have evidence of subclinical inflammation, hypoadiponectinemia, and early vascular dysfunction; this population may be at increased risk of developing CVD.

Adiponectin↗

Patterns of pregnancy-related hypertension in black and white women.

OBJECTIVE: To determine whether the higher rate of preeclampsia previously reported in Black women is attributable to a higher rate of chronic hypertension in that group. METHODS: Rates and severity of pregnancy-related hypertensive disease in Black and White women with and without chronic hypertension were reviewed from the medical records of our institution. RESULTS: Of 1,355 records reviewed, evidence of hypertensive disease was noted in 101 singleton pregnancies. Hypertension during pregnancy occurred in 7.4% of Black and 7.4% of White women. Among women with hypertension in pregnancy but no chronic hypertension, Blacks were more likely to be diagnosed with preeclampsia (78 vs. 53%, p=0.04) and more likely to have had systolic blood pressures >160 mmHg (43 vs. 17%, p=0.01). However, the rates of severe preeclampsia were similar in Black and White women since Whites were more likely to be diagnosed with severe preeclampsia in the absence of very high systolic blood pressures. Black multiparous patients with hypertension were three times more likely than White multiparous patients to be diagnosed with preeclampsia (80 vs. 27%, p=0.01). Conclusions. In our population, Black women with hypertension in pregnancy in the absence of chronic hypertension were more likely to be diagnosed with preeclampsia than were White women. This finding suggests that the higher rate of preeclampsia among Black women is not completely explained by higher rates of chronic hypertension in that group.

Adult↗

The renin-aldosterone response to stimulation and suppression during normal pregnancy.

OBJECTIVE: During normal pregnancy, studies have shown increased activity of the renin-angiotensin-aldosterone system (RAAS) and a dissociation of plasma renin activity (PRA) and aldosterone (Aldo) evidenced by a greater increase in Aldo relative to PRA. The aims of this study were to examine the RAAS response to stimulation by upright posture and suppression by saline infusion and to investigate the PRA-Aldo dissociation under these two conditions. METHODS: We studied 24 healthy normotensive women (mean+/-standard error of mean, ages 29+/-1 yrs) in sodium (Na) balance in the second and third trimesters and postpartum. Subjects underwent a 24-hour urine collection which was analyzed for Na, norepinephrine (NE), epinephrine (Epi), and dopamine (DA); a posture study with analysis of blood pressure (BP), PRA, Aldo, NE, Epi, DA, and cortisol; and a 0.9% NaCl infusion study (500 mL/hr for 3 hrs) with analysis of BP, PRA, Aldo, cortisol, and digitalis-like factor (DLF). Analyses included paired t tests to compare posture and saline responses, repeated measures to compare across periods, and percent change to evaluate the PRA-Aldo dissociation. RESULTS: During pregnancy, PRA, Aldo, BP, catecholamines, and cortisol levels were significantly greater in upright than left lateral decubitus (LLD) posture, and the percent change in Aldo was significantly greater than the percent change in PRA. During pregnancy in response to saline infusion, BP did not change; the PRA and Aldo significantly decreased; the percent change in Aldo was significantly greater than the percent change in PRA in the second trimester; and serum DLF and cortisol levels significantly decreased. CONCLUSIONS: In longitudinally studied normal pregnancy, PRA and Aldo levels were dissociated at baseline, with stimulation and, to a lesser degree, with suppression. Norepinephrine, adrenocorticotrophic hormone, and DLF may contribute to this dissociation, and clarification of these interactions may provide insight into the regulation of aldosterone during normal and hypertensive pregnancy.

Adult↗

Effects of conjugated oestrogen and droloxifene on the renin-angiotensin system, blood pressure and renal blood flow in postmenopausal women.

OBJECTIVE: The aim of this study was to evaluate the effect of conjugated equine oestrogen (CEE), and droloxifene, a selective oestrogen receptor modulator (SERM) on individual components of renin-angiotensin-aldosterone (RAAS) and blood pressure (BP) in postmenopausal women. DESIGN AND PATIENTS: Twenty-one normotensive (NT) and 10 hypertensive (HT) postmenopausal women received either CEE (0.625 mg/day) or droloxifene (60 mg/day) for 6 weeks and, after a 4-week washout, were restudied on the alternate medication. MEASUREMENTS: Hormones of the RAAS and supine BP were measured prior to and at the end of each drug treatment in all subjects. In a subgroup of the NT (n = 10), 24 h ambulatory BP was performed and renal blood flow was determined by PAH clearance both basally and in response to 45-min angiotensin II (Ang II) infusion (3 ng/kg/min). RESULTS: CEE significantly increased angiotensinogen, decreased active renin and angiotensin-converting enzyme (ACE), and maintained plasma immunoreactive (ir) angiotensin I (Ang I) levels compared to baseline. With droloxifene, angiotensinogen, active renin and Ang I remained unchanged. Both CEE and droloxifene significantly increased plasma ir-Ang II levels (pmol/l) in NT (baseline: 25.7 +/- 2.5, CEE: 36.6 +/- 3.4, droloxifene: 33.3 +/- 3.1, P < 0.002) and HT women (baseline: 17.9 +/- 2.3, CEE: 27.9 +/- 3.2, droloxifene: 25.9 +/- 4.9, P < 0.005). Renal blood flow was lower on CEE (P = 0.02) compared with baseline. Systemic BP (supine and 24-h ambulatory) was unchanged during both treatments. CONCLUSION: This study demonstrates higher circulating levels of ir-Ang II with CEE and droloxifene.

Aged↗

Preeclampsia and future cardiovascular disease: potential role of altered angiogenesis and insulin resistance.

Altered angiogenesis and insulin resistance are associated with preeclampsia and cardiovascular disease (CVD), and women with preeclampsia appear to be at increased risk of future CVD. We hypothesized that these factors are detectable in asymptomatic postpartum women with a history of preeclampsia and may represent pathophysiological mechanisms bridging preeclampsia and future CVD. We measured fasting insulin, glucose, vascular endothelial growth factor, and its circulating inhibitor, soluble fms-like tyrosine kinase (sFlt-1) in 29 normotensive women with a history of preeclampsia and 32 women with prior normotensive pregnancies at 18.0 +/- 9.7 months postpartum. The homeostasis model of insulin resistance (HOMA(IR)) [(insulin [microunits per milliliter] x glucose [millimoles per liter])/22.5] was calculated. Compared with women with normal pregnancies, women with prior preeclampsia had significantly increased levels of sFlt-1 (41.6 +/- 6.7 vs. 30.4 +/- 10.2; P < 0.01) and median HOMA(IR) (2.8 vs. 1.9; P = 0.04). Membership in the upper quartile of either sFlt-1 or HOMA(IR) was associated with prior preeclampsia (odds ratio 5.7; 95% confidence interval 1.7, 20.0; P < 0.01), and all five women in the upper quartiles of both sFlt-1 and HOMA(IR) had a history of preeclampsia. Women with a history of preeclampsia demonstrate altered expression of angiogenesis-related proteins and increased HOMA(IR) more than 1 yr postpartum. These factors may contribute to their risk of future CVD.

Adult↗

Insulin resistance and its potential role in pregnancy-induced hypertension.

New-onset hypertension (which includes preeclampsia and gestational hypertension) is a common and morbid complication of pregnancy. Many features of the insulin resistance syndrome have been associated with this condition. These include hypertension, hyperinsulinemia, glucose intolerance, obesity, and lipid abnormalities. Other accompanying abnormalities may include elevated levels of leptin, TNFalpha, tissue plasminogen activator, plasminogen activator inhibitor-1, and testosterone. The documentation of these features before the onset of hypertension in pregnancy suggests that insulin resistance or associated abnormalities may have a role in this disorder. Furthermore, the recognition that features of the insulin resistance syndrome persist many years after pregnancy among women with this condition raises the possibility that these women may have increased risk for future cardiovascular disease. These observations suggest that interventions to reduce insulin resistance may reduce the risk of both hypertension in pregnancy and later life cardiovascular complications, and warrant further study.

Cardiovascular Diseases↗

Rosiglitazone improves insulin sensitivity and lowers blood pressure in hypertensive patients.

OBJECTIVE: To examine the effect of rosiglitazone on insulin resistance and blood pressure in patients with essential hypertension, classified based on abnormalities of their renin-angiotensin system. RESEARCH DESIGN AND METHODS: A total of 24 hypertensive nondiabetic patients (age 58 +/- 6 years, BMI 30 +/- 5 kg/m2) were studied before and after rosiglitazone treatment. After 2 weeks off antihypertensive medication, subjects received a euglycemic-hyperinsulinemic clamp (40 mU. m(-2). min(-1)) with 6,6-[2H2]glucose infusion, ambulatory blood pressure monitoring, and blood tests for cardiovascular risk factors. Subjects were then placed on rosiglitazone (4 mg orally b.i.d.) and their usual antihypertensive medications (but not ACE inhibitors) for 16 weeks, and baseline tests were repeated. RESULTS: There was no change in fasting plasma glucose (83 +/- 2 vs. 82 +/- 2 mg/dl, P = 0.60), but fasting insulin decreased (16.1 +/- 1.4 vs. 12.5 +/- 0.9 micro U/ml, P < 0.01). Total glucose disposal during the clamp increased (5.0 +/- 0.4 vs. 5.9 +/- 0.5 mg. kg(-1). min(-1), P < 0.001), with no change in suppression of hepatic glucose output. There were significant decreases in mean 24-h systolic (138 +/- 2 vs. 134 +/- 2 mmHg, P < 0.02) and diastolic (85 +/- 2 vs. 80 +/- 2 mmHg, P < 0.0001) blood pressure, and the decline in systolic blood pressure was correlated with the improvement in insulin sensitivity (r = 0.59, P < 0.005). Triglycerides (135 +/- 16 vs. 89 +/- 8 mg/dl, P < 0.01), LDL cholesterol (129 +/- 6 vs. 122 +/- 8 mg/dl, P = 0.18), and HDL cholesterol (51 +/- 3 vs. 46 +/- 3 mg/dl, P < 0.02) all decreased, with no change in the LDL-to-HDL ratio. Plasminogen activator inhibitor-1 and C-reactive protein also declined significantly. CONCLUSIONS: Rosiglitazone treatment of nondiabetic hypertensive patients improves insulin sensitivity, reduces systolic and diastolic blood pressure, and induces favorable changes in markers of cardiovascular risk. Insulin sensitizers may provide cardiovascular benefits when used in the treatment of patients with hypertension.

Aged↗