Effects of hormone replacement therapy on the sympathetic nervous system and blood pressure

Hypertension is a major health problem that significantly contributes to heart disease and stroke. While most studies of hypertension have focused on men, women also experience significant hypertension-related morbidity and mortality. However, the incidence of hypertension and cardiovascular disease is significantly lower in premenopausal women compared with men until the onset of menopause, at which time cardiovascular disease incidence increases dramatically in women and eventually approaches that in men. These observations indicate that the loss of estrogen contributes to menopause-related increases in blood pressure and cardiovascular disease, and suggest that the use of estrogen hormone replacement therapy could decrease the incidence of cardiovascular disease in postmenopausal women. However, new findings from the Women’s Health Initiative study suggest that estrogen therapy has few positive benefits and some significant negative effects on the health of postmenopausal women, and these data have caused many to abandon long-term estrogen replacement therapy. Conversely, numerous clinical and basic research studies indicate that estrogen replacement therapy beneficially reduces blood pressure, thereby decreasing the incidence of hypertension and cardiovascular disease. Further, several of these studies suggest that one means by which estrogen lowers blood pressure is by decreasing sympathetic nervous system activity. This review examines the evidence supporting estrogen’s ability to modulate sympathetic nervous system tone and thereby decrease arterial pressure.     

Effects of alcohol intake and obesity on serum liver enzyme activity in obese men with mild hypertension

Abstract. Objectives. To examine the relationships between alcohol intake, obesity, plasma insulin concentration and serum activities of three liver enzymes in obese men with mild hypertension. Design. A 6-week run-in period followed by randomization to either diet treatment or antihypertensive drug treatment, lasting for 1 year. Alcohol intake was estimated using questionnaires. Plasma insulin concentration, serum activities of gamma-glutamyl transferase, and aspartate and alanine aminotransferase, respectively, were measured at entry and after 1 year. Setting. Out-patient clinic, city hospital. Patients. Sixty-four men aged 40–69 years with a body mass index > 26 kg m^?1 and with mild untreated hypertension. Exclusion criteria were alcoholism and diabetes mellitus. Sixty-one patients completed the study. Interventions. Dietary treatment was based upon weight reduction and recommendations about a low alcohol intake. Drug treatment used a stepped-care approach with atenolol as the first-choice drug. Main outcome measures. Serum activities of the liver enzymes, body weight, body mass index, alcohol intake, plasma insulin concentration. Results. Body weight decreased by 7.8 kg in the diet group and increased by 1.0 kg in the drug-treated group. Alcohol intake did not differ between the groups before or after 1 year. Serum gamma-glutamyl transferase activity correlated with alcohol consumption; it showed no significant change after weight loss. At entry, serum activities of aspartate and alanine aminotransferases correlated to plasma insulin concentration independent of body mass index. Weight reduction significantly lowered serum activities of these liver enzymes as well as plasma insulin concentrations and normalized elevated serum activity of alanine aminotransferase in a majority of the cases. Conclusion. Alcohol intake was an important determinant for elevated serum gamma-glutamyl transferase activity. The degree of obesity was a contributing factor for elevations of serum alanine aminotransferase activity. We speculate that insulin may play a role in this relationship.     

Effects of soy components on blood and liver lipids in rats fed high-cholesterol diets

AIM: To assess the effects of soy protein, isoflavone, and saponin on liver and blood lipid in rats that consumed high-cholesterol diets. METHODS: High-cholesterol diets (1%) with or without soy material were fed to 6-wk-old male Sprague-Dawley rats for 8 wk. Blood lipids, liver lipids, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) levels were measured. The in vitro bile acid-binding ability of soy materials was analyzed. RESULTS: The results of in vitro studies showed that soy protein isolate had a significantly higher bile acid-binding ability (8.4±0.8%) than soy saponin (3.1±0.7%) and isoflavone (1.3±0.4%, P<0.05). On the other hand, at the end of the experimental period, rats that consumed soy protein diets had lower GOT and GPT levels than rats that consumed casein under high-cholesterol diets. Rats that consumed soy protein also had lower total cholesterol (TC) levels in the liver than those that consumed casein under high-cholesterol diets. Rats that consumed the soy protein diet containing both saponin and isoflavone had lower hepatic TC level than those that consumed the soy protein diet without isoflavone alone. The effect of different types of proteins on triglyceride was not significant. CONCLUSION: Consumption of soy provided benefits to control lipid levels under high-cholesterol dieting conditions in this rat model of hypercholesterolemia. The major component that reduced hepatic TC was not saponin, but possibly isoflavone.     

Effects of food intake and various extrinsic hormones on portal blood flow in patients with liver cirrhosis demonstrated by pulsed Doppler with the Octoson

In the fasting state the mean portal blood flow demonstrated by the pulsed Doppler system with the Octoson in liver cirrhosis (LC) patients (velocity (PV), 10.2 +/- 3.5 (mean +/- SD) cm/sec, 7.0 +/- 2.6 cm/sec/m2; flow (PF), 579 +/- 262 ml/min, 383 +/- 184 ml/min/m2 (n = 40)) was significantly lower than that in control subjects (PV, 21.2 +/- 5.2 cm/sec, 14.7 +/- 3.9 cm/sec/m2; PF, 966 +/- 344 ml/min, 667 +/- 220 ml/min/m2 (n = 40)). Food intake increased PV by 15% and PF by 15% in LC (n = 8) and increased PV by 56%, PF by 125% in controls (n = 8). Glucagon increased PV by 30% and PF by 52% in LC (n = 10) and increased PV by 50% and PF by 120% in controls (n = 8). Secretin increased PV by 44% and PF by 75% in LC (n = 9) and increased PV by 66% and PF by 142% in controls (n = 8). Vasopressin decreased PV by 42% and PF by 54% in LC (n = 9) and decreased PV by 48% and PF by 62% in controls (n = 8). Insulin, gastrin, and prostaglandin E1 had no effect in either group.     

Effects of alendronate and hormone replacement therapy, alone and in combination, on bone mass and markers of bone turnover in elderly women with osteoporosis

The aim of the study was to compare alendronate, hormone replacement therapy (HRT), and their combination in treatment of osteoporosis in elderly postmenopausal women. Ninety patients, aged 65-80 yr (mean 71), with a T-score of bone mineral density (BMD) of 2.5 or less at either the lumbar spine or the femoral neck were randomized to receive daily 10 mg alendronate (n = 30), 2 mg estradiol plus 1 mg norethisterone acetate (n = 30) (HRT), or their combination (n = 30) for 2 yr. BMD of the lumbar spine and the upper femur was measured at baseline and after 1 and 2 yr of treatment. Urinary excretion of type I collagen aminoterminal telopeptide as related to creatinine and serum type I procollagen aminoterminal propeptide was assayed at baseline and at 6-month intervals thereafter. Increases of 9.1-11.2% in lumbar spine BMD at 2 yr were similar in the study groups. Only HRT increased femoral neck BMD statistically significantly (P < 0.0001 for a change from baseline) at both 1 (+4.9%; P =NS vs. the other groups) and 2 yr (+5.8%; P < 0.05 vs. the other groups). Total hip BMD increased similarly in all study groups. Percentage reductions in urinary type I collagen aminoterminal telopeptide in the HRT group (60.2-62.7%) were significantly smaller than those in the combination group (78.1-80.4%) (P < 0.0001-0.0069) and the alendronate-only group (72.4-76.1%) (P = 0.047 at 24 months). Serum type I procollagen aminoterminal propeptide decreased less in the HRT group (53.6-59.8%) than in the other groups [73.0-75.0% in the alendronate group (P < 0.001 at 12 months); 67.0-71.5% in the combination group (P < 0.0001 at 12 months, P = 0.013 at 24 months)]. We conclude that in elderly postmenopausal women with osteoporosis, the combination of HRT and alendronate did not offer an extra gain of bone mass over either treatment alone. In terms of BMD changes, the single treatments were equally effective, but the reductions in bone markers were less with HRT than with alendronate.     

Effects of thyroid replacement therapy on arterial blood pressure in patients with hypertension and hypothyroidism

Background Hypothyroidism is frequently accompanied by cardiac dysfunction, increased vascular resistance, and a greater prevalence of hypertension. Treatment of hypothyroidism may lead to normalization of blood pressure, although some patients may exhibit sustained hypertension. The mechanism of this condition may be the alterations in aortic stiffness. Methods Aortic stiffness was studied in 30 patients who never received treatment for hypertension or hypothyroidism, 15 patients with normal blood pressure and hypothyroidism, and 15 patients with hypertension and normal thyroid function. Thirty healthy age- and sex-matched subjects with normal thyroid function served as control subjects. Aortic diameter evaluated by M-mode echocardiography and blood pressure measured by a sphygmomanometer were used to calculate aortic stiffness index. Results Patients with high blood pressure and hypothyroidism, those with normal blood pressure and hypothyroidism, and those with hypertension and normal thyroid function showed increased aortic stiffness index (18.8 ± 6.4, 11.7 ± 3.5, and 19.2 ± 5.3 vs 9.5 ± 2.7; P < .001) compared with control subjects. In 15 patients with hypertension and hypothyroidism, levothyroxine therapy showed only a small decrease in blood pressure (151/105 ± 9/9 mm Hg, group A). The remaining 15 patients showed complete normalization of blood pressure (118/83 ± 8/3 mm Hg, group B). Aortic stiffness index was increased in group A compared with group B both before and after treatment (before, 24.0 ± 4.1 vs 13.7 ± 3.2; and after, 22.3 ± 4.2 vs 11.1 ± 2.9; P < .001 for both comparisons). Felodipine was given to patients in group A after levothyroxine was administered, resulting in normalization of blood pressure and a significant decrease of aortic stiffness index (P < .001). Aortic stiffness index was decreased in patients with hypothyroidism and hypertension after administration of levothyroxine (9.5 ± 2.2; P < .001) and felodipine (14.5 ± 7.5; P < .001) therapy, respectively. Percent changes in systolic blood pressure showed a significant correlation with percent changes in aortic stiffness index in all patients (r = 0.65, P < .001). After multivariate adjustment, aortic stiffness index (odds ratio = 1.9932; confidence interval = 1.1481 to 3.4605) was significantly associated with incomplete normalization of blood pressure. Conclusions Patients with hypertension and hypothyroidism have increased aortic stiffness. Aortic stiffness is decreased in all patients, whereas hypertension is completely reversible in 50% of patients by hormone replacement therapy. Sustained hypertension may be due to increased aortic stiffness. (Am Heart J 2002;143:718-24.)     

Effects of hormone replacement therapy on ambulatory blood pressure and vascular responses in normotensive women

The effects of chronic oestrogen replacement therapy (ERT) (conjugated equine oestrogen 0.625 mg/day) and combined oestrogen and progestogen replacement therapy (HRT) (ERT plus continuous medroxyprogesterone acetate 5 mg/day) on 24-h ambulatory blood pressure recordings, forearm vascular resistance (FVR) and FVR responses to noradrenaline, angiotensin II, acetylcholine and nitroprusside were studied in 17 normotensive postmenopausal women in a 3-month randomized, double-blind, placebo-controlled crossover trial with 1 month of therapy in each treatment arm. During the last few days of each 1-month treatment period, the subjects underwent 24-h ambulatory blood pressure recordings and measurements of FVR responses. ERT and HRT reduced mean 24-h diastolic blood pressure by 4 and 5 mmHg, systolic blood pressure by 6 and 9 mmHg and mean 24-h heart rate by 5 and 3 beats/min, respectively for ERT and HRT (p < 0.05). Basal FVR was reduced by approximately 18% by ERT and HRT, but FVR responses to noradrenaline, angiotensin II, acetylcholine and nitroprusside were unaffected. ERT and HRT therapy for 1 month lowers blood pressure and basal FVR, but does not appear to influence FVR responses to acetylcholine, nitroprusside, noradrenaline and angiotensin II.     

Effects of dehydroepiandrosterone replacement therapy on bone mineral density in older adults: a randomized, controlled trial

CONTEXT: Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) decrease with aging and are important androgen and estrogen precursors in older adults. Declines in DHEAS with aging may contribute to physiological changes that are sex hormone dependent. OBJECTIVE: The aim was to determine whether DHEA replacement increases bone mineral density (BMD) and fat-free mass. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blinded, controlled trial was conducted at an academic research institution. Participants were 70 women and 70 men, aged 60-88 yr, with low serum DHEAS levels. INTERVENTION: The intervention was oral DHEA 50 mg/d or placebo for 12 months. MEASUREMENTS: BMD, fat mass, and fat-free mass were measured before and after intervention. RESULTS: Intent-to-treat analyses revealed trends for DHEA to increase BMD more than placebo at the total hip (1.0%, P = 0.05), trochanter (1.2%, P = 0.06), and shaft (1.2%, P = 0.05). In women only, DHEA increased lumbar spine BMD (2.2%, P = 0.04; sex-by-treatment interaction, P = 0.05). In secondary compliance analyses, BMD increases in hip regions were significant (1.2-1.6%; all P < 0.02) in the DHEA group. There were no significant effects of DHEA on fat or fat-free mass in intent-to-treat or compliance analyses. CONCLUSIONS: DHEA replacement therapy for 1 yr improved hip BMD in older adults and spine BMD in older women. Because there have been few randomized, controlled trials of the effects of DHEA therapy, these findings support the need for further investigations of the benefits and risks of DHEA replacement and the mechanisms for its actions.     

Effect of satiety center damage on food intake,blood glucose and gastric secretion in dogs

Goldthioglucose is capable of damaging the ventromedial hypothalamus (satiety center) and inducing obesity in dogs, similar to the effects reported in mice and rats. Body weight was increased at a rate of 10% or more in 51% of the goldthioglucose-treated dogs during an 8-week period. Daily food intake was also increased, significantly, as high as 20% or more, in 68% of the goldthioglucose-treated dogs. Fasting blood-glucose levels did not show any change in obese animals, but blood glucose utilization increased significantly as compared with control animals. The sensitivity of glucose regulating mechanisms to insulin was enhanced by goldthioglucose treatment. Fasting gastric secretion in Pavlov pouch dogs, increased in volume and acidity, above preinjection levels of goldthioglucose, but this effect was not seen in Heidenhain pouch dogs.     

Effects of alloxan diabetes and insulin on morphology and certain functional activities of mitochondria of the rat liver and heart

Summary The authors studied the ultrastructural appearance and metabolic behaviour of mitochondria in the liver and heart of rats suffering from alloxan diabetes. Liver mitochondria did not show significant morphological and biochemical changes compared to normal, whereas heart mitochondria were decreased in number, their structure was altered and the phosphorylating activity was obviously impaired. Insulin treatment significantly improved the P/O ratio although, as far as the myocardium was concerned, it could not normalize it. The differences in behaviour of liver and heart mitochondria related to the changes of lipid and carbohydrate metabolism and to the disordered ion balance occurring in this experimental endocrine disease, are discussed. This work was in part supported by a grant from theConsiglio Nazionale delle Ricerche (Rome).     

Effects of biotin, with or without sodium nitrite, on weight, food and fluid intake, and on methemoglobin, lactate and lipids in the blood of rats

The effects of biotin deprivation on various plasma constituents were studied in male Sprague-Dawley rats, some of which were also treated with sodium nitrate (NaNO2), extra niacin or linoleate. A basal diet containing 15% pork fat (lard), 30% egg white and sucrose, was fed for 7 weeks, with or without a weekly supplement of 150 microgram biotin and the other substances mentioned. Biotin-deprived rats ate significantly less food, gained less weight and had lower food efficiency ratios than biotin-supplemented rats. Rats given NaNO2 in the drinking water had significantly higher levels of methemoglobin than those without it; values were highest when extra niacin or linoleate was added to the diet. Lactate was highest in deprived rats and was lowest in rats supplemented with biotin alone. Blood lipids were higher with than without biotin, regardless of NaNO2. Levels of phospholipids and triglycerides were highest when extra niacin was added to the diet. Further studies are needed to define the role of biotin in oxidation-reduction reactions and in regulation of lipid metabolism.     

Effects on growth and body composition of androgen deprivation by castration or autoimmunization to LH-releasing hormone in the male rat under conditions of controlled food intake

The effects of endogenous gonadal hormones on the regulation of body composition and energy retention have been investigated under conditions of controlled food intake. Male and female rats were fed the same amount from weaning to 82 days of age. The carcases of males contained more protein, less lipid and yielded more ash than females, but they had the same amount of total energy in their carcases as females. In a second experiment, male rats were sham-operated or castrated at 19 days and then fed equal amounts from weaning. At 40 days, intact and castrated rats did not differ in total carcase energy content nor in carcase composition. At 82 days the carcases of intact rats had more protein but had retained the same amount of energy as castrated rats. By 131 days, the difference in protein content was larger and intact rats had less carcase lipid, less carcase energy and gave less ash than castrated rats. At the same age and with a similar food intake, the differences in carcase composition between intact males and females were considerably larger than between intact and castrated males. In a third experiment, male rats were sham-operated or castrated at 1 day post partum and fed the same amount as in the second experiment from weaning to 82 days. Both sham-castrated and castrated rats grew less well than rats operated on at 19 days. The differences in carcase composition between intact and castrated rats were in the same direction but of greater magnitude than in rats operated at the later age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hormone replacement therapy on office and ambulatory blood pressure in Japanese hypertensive postmenopausal women.

No study has demonstrated that hormone replacement therapy (HRT) affects blood pressure (BP) measured by 24-h ambulatory blood pressure monitoring (ABPM) in Japanese postmenopausal women (PMW) with normotension or mild-to-moderate essential hypertension. In the present study, we examined the effects of HRT on office BP and 24-h ambulatory blood pressure (ABP) in Japanese hypertensive or normotensive PMW. Thirty-one hypertensive (HT-HRT group) and 17 normotensive PMW (NT-HRT group) received HRT (0.625 mg of conjugated equine estrogen combined with 2.5 mg of medroxyprogesterone acetate) orally for 12 months, and 30 hypertensive (HT-Control group) and 19 normotensive PMW (NT-Control group) did not receive HRT. In all of the hypertensive PMW, BP was controlled by a variety of antihypertensive drugs before starting HRT. The hypertensive PMW were divided into two groups according to the results of ABP before HRT: nondippers (those without a diurnal change in BP) and dippers (those with a diurnal change in BP). In all patients, office BP measurements and 24-h ABPM were performed before and 12 months after the start of HRT. HRT did not change either the office or the 24-h ambulatory systolic, diastolic, or mean BP in any of the groups. Therefore, HRT did not significantly alter the proportion of nondippers. We conclude that with respect to BP, HRT might not be harmful in hypertensive PMW whose BP has been well-controlled prior to the initiation of HRT, as well as in normotensive PMW.     

Effects of 20-mg oestradiol implant therapy on bone mineral density, fat distribution and muscle mass in postmenopausal women

This 64-week prospective cohort trial evaluated the effects of 20-mg oestradiol implants, replaced every 4 months, in healthy postmenopausal women aged 45-65 years. Of 20 implant and 14 control subjects who remained in the trial at 32 weeks, 13 implant and seven controls continued to 64 weeks, with no baseline differences between completing and dropout subjects. At 64 weeks, implant subjects displayed increases of 5.4-7.6% in spine and hip bone mineral density ( p<0.05 versus controls). The abdominal fat-to-lean soft tissue ratio decreased by 18% in implant subjects ( p<0.001), but did not change in controls ( p<0.05 implants versus controls). Neither group displayed significant changes in weight, %fat or appendicular skeletal muscle mass. The 32-week data were consistent with these results. Hence, oestradiol implant therapy can reduce abdominal adiposity and could lower the risk of obesity-related metabolic disorders.     

Isolation of c-kit receptor-expressing cells from bone marrow, peripheral blood, and fetal liver: functional properties and composite antigenic profile.

To define the cellular targets for c-kit ligand (KL) and to study their functional properties and composite antigenic profile, we isolated cells expressing c-kit receptor (KR) from bone marrow (BM), peripheral blood, and fetal liver (FL) using immunoadherence to a recently obtained antibody (SR-1) against the human KR. Cells isolated by this approach (designated SR-1Ad) have the morphology of blasts and represent 1% to 4% of the original BM or FL populations. SR-1Ad cells from either source are highly enriched in progenitors (12% to 73%) and respond to KL in distinct patterns. In SR-1Ad cells from BM, the greatest impact of KL stimulation is on burst-forming units-erythroid (BFU-E), whereas in SR1-Ad cells from FL, the most significant KL effect is on a mixed erythroid/nonerythroid progenitor (erythroid/macrophage, colony-forming unit-mix [CFU-Mix]). When antibody SR-1 is continually present in culture, it neutralizes the effects of added KL. Furthermore, in the absence of added KL, it greatly diminishes the erythropoietin- and interleukin-3-dependent BFU-E growth in BM; whereas in FL, a wider spectrum of inhibition is observed, with CFU-Mix most severely curtailed. SR-1Ad cells coexpress other progenitor-associated antigens in a combination reflecting the dominant presence of erythroid progenitors (high expression of CD34, DR, CD38, and Ep-1; low expression of CD33). Several cytoadhesion molecules, ie, alpha L/beta 2 and alpha 4/beta 1 integrins, and intercellular adhesion molecule 1 and homing cell adhesion molecule 1, are also coexpressed. Our data provide new information on the isolation and characterization of KR expressing cells from normal, adult, and fetal hematopoietic tissues. On these biologically relevant target cells, the impact of ligand-induced stimulation or antibody-mediated ablation of KR function has been gauged.