Preeclampsia -- searching for the cause.
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Biomedical subjects
Ellen W Seely
Publications and source records attributed to Ellen W Seely.
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.
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Clinical problem-solving. Mind the gap.
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Bilirubin↗
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.
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