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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that juvenile Sprague-Dawley rats, fed a diet in which complex carbohydrates are replaced by sucrose, develop insulin resistance and hypertension. These conditions develop despite the absence of genetic predisposition to either. When studied with the euglycemic hyperinsulinemic clamp technique, these rats have reduced insulin-stimulated glucose utilization, but normal suppression of hepatic glucose output. In the young sucrose-fed rats, it was noted that the degree of blood pressure elevation was greater in males than in females. The purpose of this study was to test the hypothesis that estrogen withdrawal increases insulin resistance and hypertension. Female rats were randomized at weaning (3 weeks of life) to receive control diet or sucrose diet. Animals were assessed with weekly weight and indirect tail-cuff blood pressure. At 8 weeks of life, the sucrose-fed rats were randomized to receive bilateral oophorectomy or sham surgery (anesthesia and uterine horn exposure without removal of the ovaries). At 13 to 14 weeks of life, all animals were fasted overnight, and had an oral glucose tolerance test while conscious. Weight and weight gain were not different among the groups over the 11 week study period. Animals fed the sucrose diet developed significantly higher blood pressure than animals fed the control diet; oophorectomized animals had higher blood pressure than sham-operated animals (P <.0001). Sucrose-fed oophorectomized animals developed fasting and glucose-stimulated hyperinsulinemia. Estrogen withdrawal augments blood pressure in juvenile rats made insulin resistant and hypertensive with a sucrose diet. Estrogen withdrawal in these animals also induces fasting and glucose-stimulated hyperinsulinemia, which are signs of worsening insulin resistance. Androgen:estrogen imbalance increases metabolic dysfunction and worsens hypertension in this animal model.
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PMID:Effect of estrogen withdrawal on blood pressure and insulin resistance in sucrose-fed juvenile rats. 897 91

A review of the recent epidemiologic evidence indicates that use of low-dose combined oral contraceptives (OCs) is not associated with any clinically significant increase in risk of myocardial infarction (MI) or stroke, including for smokers under 35 years of age. Even if the small elevation in risk for these diseases is assumed to be causal, the incidence of both MI and stroke associated with use of OCs containing under 50 mcg of ethinyl estradiol would be only 2 per 100,000 events per year. This risk would be even lower for women under 35 years of age who do not smoke and have no history of hypertension. Two new reports have identified even lower relative risks of MI and stroke among users of OCs containing the progestins desogestrel and gestodene compared with users of second-generation OCs. However, four additional epidemiologic studies have revealed a two-fold increased risk of non-fatal venous thromboembolism for OCs containing desogestrel or gestodene compared to levonorgestrel; the excess risk is about 15 per 100,000 events per year. Until there is a biologic explanation of the greater thromboembolism risk in users of third-generation OCs, this association should not be viewed as causal and no change in OC prescribing practices is warranted for either current or new acceptors. However, smokers over 35 years of age should not use any combination OCs.
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PMID:Estrogen and progestin components of oral contraceptives: relationship to vascular disease. 922 Feb 22

We studied 16 postmenopausal women with mild to moderate hypertension according to a randomized, double-blind protocol. They received patches of transdermal estradiol-17beta rated to deliver 100 mg/day of substance or matched placebo. A 24-hour ambulatory blood pressure (BP) monitoring was performed at baseline and after drug administrations. Our data show that estradiol-17beta exerts beneficial effects, both in lowering elevated BP levels and in maintaining a uniform BP control over 24 hours. Estrogen replacement therapy could be considered when significant changes in BP occur during the postmenopausal period.
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PMID:Effects of acute administration of transdermal estrogen on postmenopausal women with systemic hypertension. 929 4

Estrogen treatment affects the hepatic synthesis and/or secretion of several proteins involved in clinically important pathological processes such as atherosclerosis, hypertension, and thrombosis. The endocrine regulation of the estrogen receptor (ER) concentration in primary cultures of rat hepatocytes was studied. Human growth hormone (hGH) and dexamethasone (DEX) in combination increased ER concentration 6-fold and ER mRNA levels 2.5-fold. These effects were not significantly different from those observed after treatment with the purely somatogenic bovine growth hormone (GH) in combination with DEX. Treatment with the lactogen ovine prolactin in the presence or absence of DEX did not significantly affect ER or ER mRNA concentrations. Triiodothyronine treatment at the most effective concentration (50 nM) increased ER and ER mRNA levels twofold. Medium supplementation with estradiol (0.1 nM) throughout the experiment did not affect the response to treatment with hGH and DEX. Treatment with high concentrations of ethinylestradiol in combination with hGH and DEX, however, increased the ER level twice as much as hGH and DEX without addition of estradiol or ethinylestradiol, whereas the ER mRNA concentration was the same in both the GH+DEX group and GH+ DEX+ (estradiol or ethinylestradiol) groups. These data indicate the importance of GH in combination with glucocorticoids for the maintenance of ER concentrations in the rat liver. Thyroid hormones may be of some, although minor importance, whereas the data suggest that prolactin is not directly involved in hepatic ER regulation.
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PMID:Hormonal regulation of the estrogen receptor in primary cultures of hepatocytes from female rats. 938 11

Estrogens are reported to provide protection against the development of cardiovascular disease in women, but the mechanisms underlying these effects are not well defined. We hypothesized that estrogen might reduce neural cardiovascular tone. We therefore studied responses to exogenous norepinephrine and norepinephrine spillover in 12 perimenopausal women randomized to 8 weeks of estrogen supplementation (estradiol valerate, 2 mg daily, n=7) or placebo (n=5). Forearm blood flow was measured by venous occlusion plethysmography, and vasoactive agents were infused through a brachial artery cannula in doses that did not influence blood pressure or heart rate. Total body and forearm norepinephrine spillover were measured by radiotracer methodology. Forearm vasoconstrictor responses to norepinephrine (25, 50, and 100 ng/min) were attenuated after estrogen supplementation (P=.002). Vasoconstrictor responses to angiotensin II (8, 16, and 32 ng/min) were unchanged postestrogen. There was a significant reduction in total body spillover of norepinephrine after estrogen supplementation (pre-estrogen, 700+/-152; postestrogen, 439+/-150 ng/min; P<.05), but there was no change after placebo. Total body clearance and forearm spillover of norepinephrine were unchanged by either estrogen or placebo. Estrogen supplementation also significantly decreased both systolic and diastolic blood pressures. Therefore, estrogen supplementation in perimenopausal women selectively attenuates vasoconstrictor responses to norepinephrine and reduces total body norepinephrine spillover, which is an index of sympathetic neural activity.
Hypertension 1997 Dec
PMID:Estrogen supplementation decreases norepinephrine-induced vasoconstriction and total body norepinephrine spillover in perimenopausal women. 940 79

In pursuit of the hypothesis that estrogen shifts the vasoconstrictor-vasodilator balance of the renin-angiotensin system, we investigated the cardiovascular responses to administration of angiotensin-(1-7) [ANG-(1-7)] and angiotensin II (ANG II) in female transgenic (mRen2)27-positive [Tg(+)] and -negative [Tg(-)] rats in the presence and absence of 3 wk of estrogen replacement therapy. Fifty-three female Tg(-) and Tg(+) rats were oophorectomized and received either 17 beta-estradiol (1.5 mg/rat s.c. for 3 wk) or vehicle. At the end of 3 wk of estrogen treatment, mean blood pressure was lowered in freely moving chronically cannulated Tg(+) (159 +/- 4 vs. 145 +/- 5 mmHg, P < 0.05) and Tg(-) (119 +/- 4 vs. 108 +/- 2 mmHg, P < 0.05) rats. Moreover, the magnitude of the depressor component of the biphasic response to ANG-(1-7) was significantly enhanced in estrogen-treated Tg(+) rats, whereas the pressor component to ANG-(1-7) was attenuated in both Tg(+) and Tg(-) rats. Estrogen replacement significantly attenuated the pressor response to ANG II in both Tg(+) and Tg(-) rats. In addition, estrogen replacement therapy significantly reduced plasma ANG-converting enzyme activity in association with a reduction in circulating levels of ANG II. Tissue levels (kidney and aorta) of ANG-converting enzyme were also reduced with chronic estrogen replacement therapy. On the other hand, estrogen augmented the levels of plasma ANG-(1-7) in Tg(+) animals. Plasma renin activity was unchanged with estrogen treatment. These findings provide the first evidence demonstrating that estrogen is protective against hypertension, possibly by amplifying the vasodilator contributions of ANG-(1-7), while reducing the formation and vasoconstrictor actions of ANG II.
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PMID:Estrogen protects transgenic hypertensive rats by shifting the vasoconstrictor-vasodilator balance of RAS. 943 44

Estrogens have been found to reduce the incidence of cardiovascular disease that has been ascribed in part to an increased expression and/or activity of the vasoprotective endothelial NO synthase (NOS III). Some reports have shown that the level of expression of this constitutive enzyme can be upregulated by estrogens. The current study investigates the molecular mechanism of the NOS III upregulation in human endothelial EA.hy 926 cells. Incubation of EA.hy 926 cells with 17beta-estradiol or the more stable 17alpha-ethinyl estradiol enhanced NOS III mRNA and protein expression up to 1.8-fold, without changing the stability of the NOS III mRNA. There was no enhancement of NOS III mRNA after incubation of EA.hy 926 cells with testosterone, progesterone, or dihydrocortisol or when 17alpha-ethinyl estradiol was added together with the estrogen antagonist RU58668, indicating a specific estrogenic response. Nuclear run-on assays indicated that the increase in NOS III mRNA is the result of an estrogen-induced enhancement of NOS III gene transcription. In transient transfection experiments using a 1.6 kb human NOS III promoter fragment (which contains no bona fide estrogen-responsive element, ERE), basal promoter activity was enhanced 1.7-fold by 17alpha-ethinyl estradiol. In electrophoretic mobility shift assays, nuclear extracts from estrogen-incubated EA.hy 926 cells showed no enhanced binding activity either for the ERE-like motif in the human NOS III promoter or for transcription factor GATA. However, binding of transcription factor Sp1 (which is essential for the activity of the human NOS III promoter) was significantly enhanced by estrogens. These data suggest that the estrogen stimulation of the NOS III promoter could be mediated in part by an increased activity of transcription factor Sp1.
Hypertension 1998 Feb
PMID:Estrogens increase transcription of the human endothelial NO synthase gene: analysis of the transcription factors involved. 946 Dec 25

This article discusses the risk factors for coronary heart disease (CHD)--the leading cause of death in the US--in women. Studies have shown that cigarette smoking more than doubles CHD incidence and increases CHD mortality by 70%. A cohort study among more than 121,000 female nurses in the US revealed that the risk of CHD was 6 times greater in heavy smokers than nonsmokers. The level of blood cholesterol is also a strong risk factor for CHD: levels of high-density lipoprotein (HDL) cholesterol are inversely associated with the risk of CHD. Thus, lowering low-density lipoprotein (LDL) and increasing HDL cholesterol levels reduce CHD risk in both men and women. Hypertension is a risk factor which responds well to pharmacologic treatment, and increasing levels of physical activity were proven to decrease CHD risk in numerous studies. Meanwhile, obesity, which is prevalent in the US, worsens other coronary risk factors such as hypertension, diabetes, and hypercholesterolemia. A study showed that overweight women (body mass index values 29) are at 3 times the risk for CHD as those with body mass index values less than 21. Diabetes mellitus is another CHD risk factor which is stronger in women than in men, and CHD death rates are 3-7 times greater among diabetic than nondiabetic women. Other studies revealed that women who consumed alcohol in moderation (10-15 g of alcohol per day) had a 40% lower risk of CHD compared with nondrinkers. There is a significant relationship between combined oral contraceptive and cigarette use and increased risk of CHD. Estrogen replacement therapy, low-dose aspirin, and antioxidant vitamins have been proven in studies to reduce the risk of CHD in women.
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PMID:Risk factors for coronary heart disease in women. 950 75

To assess the influence of oral contraceptives (OC) on the risk for venous thromboembolism (VTE) in young women, a 5-year case-control study including all women 15-44 years old suffering a first deep venous thrombosis or a first pulmonary embolism from all Danish hospitals, along with 1200 control subjects during the period 1994-1995, was conducted. Of 586 patient and 1200 control subject questionnaires sent out, 523 patient (89.2%) and 1074 control (89.5%) questionnaires were returned with an agreement to participate. After exclusion of women with nonvalid diagnoses, women who were pregnant, and women with previous VTE or acute myocardial infarction (AMI), 375 patients and 1041 control subjects were available for analysis. Potential tested confounders included: body mass index, length of OC use, family history of VTE, AMI, or stroke, smoking habits, coagulopathies, diabetes, years of schooling, certainty of diagnosis, previous births, and treated hypertension during any pregnancy. A multivariate analysis was performed. Estrogen dose had no influence on the risk for VTE. The risk for VTE among current users of OC was primarily influenced by duration of use, with significantly decreasing odds ratios (OR) over time: < 1 year; 5.1 (3.1-8.5); 1-5 years; 2.5 (1.6-4.1); and > 5 years; 2.1 (1.5-3.1), all compared with those for nonusers of OC. This trend was still significant after adjustment for progestin types. Without adjustment for duration of use, current users of OC with second generation (levonorgestrel or norgestimate) and third generation (desogestrel or gestodene) progestins had OR of 1.8 (1.1-2.9) and 3.2 (2.3-4.4), respectively. After correction for duration of use, however, no significant differences were found between users of OC with different types of progestins. In conclusion, OC increase the risk for VTE significantly. The risk among current users of OC is primarily influenced by duration of use. No difference in risk was found according to estrogen dose, and the difference in risk between different types of progestins was not statistically significant after adjustment for duration of use.
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PMID:Oral contraceptives and venous thromboembolism. A case-control study. 967 36

The Heart and Estrogen/progestin Replacement Study (HERS) is a randomized, double-blind, placebo-controlled trial designed to test the efficacy and safety of estrogen plus progestin therapy for prevention of recurrent coronary heart disease (CHD) events in women. The participants are postmenopausal women with a uterus and with CHD as evidenced by prior myocardial infarction, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, or other mechanical revascularization or at least 50% occlusion of a major coronary artery. Between February 1993 and September 1994, 20 HERS centers recruited and randomized 2763 women. Participants ranged in age from 44 to 79 years, with a mean age of 66.7 (SD 6.7) years. Most participants were white (89%), married (57%), and had completed high school or some college (80%). As expected, the prevalence of coronary risk factors was high: 62% were past or current smokers, 59% had hypertension, 90% had serum LDL-cholesterol of 100 mg/dL or higher, and 23% had diabetes. Each woman was randomly assigned to receive one tablet containing 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate daily or an identical placebo. Participants will be evaluated every 4 months for an average of 4.2 years for the occurrence of CHD events (CHD death and nonfatal myocardial infarction). We will also assess other major CHD endpoints, including revascularization and hospitalization for unstable angina. The primary analysis will compare the rate of CHD events in women assigned to active treatment with the rate in those assigned to placebo. The trial was designed to have power greater than 90% to detect a 35% reduction in the incidence of CHD events, assuming a 50% lag in effect for 2 years and a 5% annual event rate in the placebo group. The design, analysis, and conduct of the study are controlled by the Steering Committee of Principal Investigators and coordinated at the University of California, San Francisco. HERS is the largest trial of any intervention to reduce the risk of recurrent CHD events in women with heart disease and is the first controlled trial to seek evidence of the efficacy and safety of postmenopausal hormone therapy to prevent recurrent CHD events.
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PMID:Heart and Estrogen/progestin Replacement Study (HERS): design, methods, and baseline characteristics. 968 9


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