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

The fetal environment is now recognized as a key determinant of the adult phenotype, being linked to development of diseases, including hypertension, as well as the timing of puberty. Such links may be related, in part, to the level of fetal exposure to maternal glucocorticoids in utero, which is normally regulated by placental expression of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD). The present study examined whether manipulation of fetal glucocorticoid exposure, either directly or indirectly via 11beta-HSD inhibition, influences the subsequent timing of puberty. Administration of dexamethasone acetate at low (LDEX, 0.25 microg/ml drinking water) or high doses (HDEX, 1 microg/ml) or carbenoxolone (CBX, 2 x 10 mg/day, sc; an inhibitor of 11beta-HSD) to pregnant rats from day 13 to term (day 23) reduced offspring birthweight (LDEX: 9%; HDEX: 27%; CBX: 8%) and resulted in a subsequent delay in the onset of puberty in females (control: 41.4 +/- 0.5; LDEX: 44.8 +/- 0.7; HDEX: 48.5 +/- 0.4; CBX: 43.6 +/- 0.5 days). Importantly, the effects of CBX were not observed in the absence of maternal adrenals, indicating that they were mediated by increased fetal exposure to endogenous maternal glucocorticoids. In contrast, maternal treatment with metyrapone (MET; an inhibitor of glucocorticoid synthesis; 500 microg/ml drinking water from day 13) increased birthweight by 5% and advanced puberty onset in male offspring (control: 48.8 +/- 1.0; MET: 45.7 +/- 0.8 days). Changes in the timing of puberty onset were not attributable to changes in either bodyweight at puberty or peripubertal plasma leptin concentrations. Peripubertal plasma LH was also unaffected in animals with delayed puberty but was elevated in male offspring of MET-treated mothers. Collectively, these results demonstrate that fetal glucocorticoid exposure is an important determinant of the timing of puberty onset in postnatal life, and that this effect is operable within the normal physiological range of glucocorticoid concentrations.
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PMID:Increased fetal glucocorticoid exposure delays puberty onset in postnatal life. 1087 42

Environmental factors and diet are generally believed to be accelerators of obesity and hypertension, but they are not the underlying cause. Our animal model of obesity and hypertension is based on the observation that impaired fetal growth has long-term clinical consequences that are induced by fetal programming. Using fetal undernutrition throughout pregnancy, we investigated whether the effects of fetal programming on adult obesity and hypertension are mediated by changes in insulin and leptin action and whether increased appetite may be a behavioral trigger of adult disease. Virgin Wistar rats were time mated and randomly assigned to receive food either ad libitum (AD group) or at 30% of ad libitum intake, or undernutrition (UN group). Offspring from UN mothers were significantly smaller at birth than AD offspring. At weaning, offspring were assigned to one of two diets [a control diet or a hypercaloric (30% fat) diet]. Food intake in offspring from UN mothers was significantly elevated at an early postnatal age. It increased further with advancing age and was amplified by hypercaloric nutrition. UN offspring also showed elevated systolic blood pressure and markedly increased fasting plasma insulin and leptin concentrations. This study is the first to demonstrate that profound adult hyperphagia is a consequence of fetal programming and a key contributing factor in adult pathophysiology. We hypothesize that hyperinsulinism and hyperleptinemia play a key role in the etiology of hyperphagia, obesity, and hypertension as a consequence of altered fetal development.
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PMID:Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. 1089 26

Our long-term objective is to identify genes whose expression results in hypertension and in phenotypic changes that may contribute to hypertension. The purpose of the present study was to describe evidence for the heritability of hypertension-related phenotypes in hypertensive, hyperlipidemic black sib pairs. Outpatient anthropomorphic measurements were obtained in >200 affected sib pairs. In addition, 68 of these sib pairs were studied under controlled, standardized conditions at an inpatient clinical research center while off both antihypertensive and lipid-lowering medications. Heritability was estimated on the basis of sib-sib correlations and with an association model. Higher heritability estimates for blood pressure were observed with multiple measurements averaged over 24 hours than with measurements at a single time point, and heritability estimates for nighttime blood pressures were higher than those for daytime blood pressures. Heritability estimates for several of the phenotypes were augmented by obtaining measurements in response to a standardized stimulus, including (1) blood pressure responses to the assumption of upright posture, standardized psychological stress, and norepinephrine infusion; (2) plasma renin, aldosterone, epinephrine, and cAMP and cGMP responses to the assumption of upright posture; (3) para-aminohippurate and inulin clearances in response to norepinephrine infusion; and (4) plasma arginine vasopressin in response to NaCl infusion. High heritability estimates were also observed for various measures of body size and body fat, left ventricular size, cardiac index, stroke volume, total peripheral resistance, and serum concentrations of LDL and HDL cholesterol and leptin. These heritability estimates identify the hypertension-related phenotypes that may facilitate the identification of specific genetic determinants of hypertension in blacks with hyperlipidemia.
Hypertension 2000 Jul
PMID:Genetic determinants of hypertension: identification of candidate phenotypes. 1090 5

There is substantial evidence that obesity is a prime risk factor for the development of hypertension. Although hyperinsulinemia and an increased activity of the sympathetic nervous system have been implicated in the pathogenesis of "obesity hypertension," their effects on energy metabolism have not been studied thus far. In the present study, we therefore examined resting metabolic rate (RMR) and basal substrate oxidation in subjects with obesity and obesity-related hypertension. A total of 166 subjects were characterized for RMR and basal substrate use through indirect calorimetry. Blood pressure was measured at rest and with 24-hour ambulatory monitoring. Blood samples were collected for the measurement of plasma catecholamines, leptin, and the insulin response to an oral glucose load. In our study population, 116 subjects were defined as hypertensive and 91 were defined as obese. Hypertensive patients under beta-adrenergic blockade (n=42) had a significantly lower RMR than did patients without beta-blockade (P<0. 05) and were therefore excluded from further analyses. Univariate regression analysis revealed a significant relationship between RMR and body fat mass, as well as body fat-free mass, in both groups. Compared with obese normotensive control subjects (n=27), obese hypertensives (n=43) had a 9% higher RMR (P<0.05), higher plasma catecholamine (P<0.05) and leptin (P<0.05) levels, and an increased insulin response to oral glucose (P<0.01). Together, these findings are compatible with the idea that chronic neurogenic and metabolic adaptations related to obesity may play a role in the development of obesity hypertension in susceptible individuals.
Hypertension 2000 Jul
PMID:Resting metabolic rate and substrate use in obesity hypertension. 1090 8

The number of patients with hypertension, obesity, diabetes, and hyperlipidemia is increasing. This tendency is observed in pregnant women, in whom many obstetrical and perinatal complications occur. The prevention of these abnormalities is important in reducing perinatal mortality and the risk of coronary disease. We established a pregnant rat model with diabetes and signs and symptoms mimicking preeclampsia. On day 6 of pregnancy, streptozotocin (STZ) or citrate buffer was injected into the tail vein. After STZ administration, plasma glucose was increased within 48 hours and sustained at a high level until day 20 of pregnancy, and plasma insulin was decreased. Fetuses from STZ-treated mothers were growth-restricted, and plasma glucose was 6-fold higher in fetuses of STZ-treated versus control rats. The systolic blood pressure, urinary protein, and hematocrit were increased significantly in STZ-treated rats. Total cholesterol and triglycerides were also elevated in STZ-treated rats, but plasma leptin levels were decreased. The STZ-induced diabetic pregnant rat model exhibited preeclampsia, hemoconcentration, hyperlipidemia, hypoleptinemia, and intrauterine growth restriction. This model closely mimics the features of human pregnancy complicated by diabetes and is useful for the basic study of the pathophysiology of pregnancy with diabetes.
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PMID:Streptozotocin-induced diabetic pregnant rats exhibit signs and symptoms mimicking preeclampsia. 1090 94

The purpose of this study was to clarify the relationships between obesity (BMI) and BP levels, leptin levels, sympathetic activity, and insulin sensitivity in a Japanese male population. In 912 young, non-diabetic, Japanese men with a wide range of BMI (16.5-33.6 kg/m2), blood pressure (BP), fasting plasma norepinephrine (NE), insulin and leptin levels were measured after an overnight fast. The cohort consisted of 603 normotensive and 309 hypertensive subjects. The study was carried out using a cross-sectional design. When the subjects were subdivided by tertile in relation to BMI, the 101 subjects in the heaviest group (BMI > 27.9 kg/m2) had a significantly higher systolic BP (p< 0.05) and pulse rate (p< 0.05) as well as higher NE (p< 0.01), insulin (p< 0.01), and leptin (p< 0.01) levels than 86 subjects in the leanest group (BMI < 22.2 kg/m2). In the whole cohort, BMI correlated with mean BP (p< 0.01), plasma NE (p< 0.05), insulin (p< 0.001) and leptin (p< 0.001). The mean BP correlated with BMI (p< 0.001), plasma NE (p< 0.01), insulin (p< 0.01) and leptin (p< 0.05). Plasma leptin levels correlated with fasting plasma insulin levels (p < 0.05), but not with plasma NE levels (NS). As analyzed by multiple regression analysis, only plasma NE (p< 0.05) and BMI (p< 0.001), but not plasma insulin levels, were significant, independent predictors of BP levels (r2=0.125, F= 10.51, p=0.0001). These results suggest that obesity (BMI) and heightened sympathetic nervous system activity contribute to BP elevation (hypertension).
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PMID:Sympathetic activity and body mass index contribute to blood pressure levels. 1091 65

Leptin, the gene product of the ob gene, is influenced by gender and insulin sensitivity. Because in human hypertension there are important endocrine-hemodynamic gender-dependent differences, we compared plasma leptin in 39 essential hypertensives (EH) and in 27 normotensive healthy subjects (HS) matched for gender, age, and fat mass. Fat mass was measured by bioelectrical impedance analysis (BIA), plasma leptin by a sensitive radioimmunoassay RIA (intraassay CV < 6%), and insulin sensitivity by the HOMA-R index. Both in essential hypertensives and in normotensive subjects plasma leptin was consistently higher in females than in males and was strictly related to fat mass. Gender differences in plasma leptin were not explained by differences in fat mass. Separate analysis of data by gender showed that leptin was significantly higher (P < .05) in hypertensive men (median, 5.4 ng/mL; interquartile range, 4.1-9.5) than in normotensive men (4.6 ng/mL, 2.6-7.4) whereas it was identical in hypertensive and normotensive women. In essential hypertensives, in a multiple regression model only fat mass, gender, and the HOMA-R index were independently linked to plasma leptin. Similarly, fat mass and gender were independent predictors of plasma leptin in normotensive subjects. In the combined group of hypertensive and normotensive men, heart rate as well as systolic and diastolic pressure were univariate predictors of leptin. However, in a multivariable model only heart rate was independently related to leptin, and neither systolic nor diastolic pressure contributed significantly to explain the variability in plasma leptin. No relationship was found between leptin and heart rate or systolic or diastolic pressure in women. These results support the notion that leptin may participate in the gender-dependent variability of human hypertension.
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PMID:Gender-dependent differences in plasma leptin in essential hypertension. 1095 Apr

Both leptin and the renin-angiotensin system (RAS) can influence the activity of the sympathetic nervous system, water and electrolyte metabolism as well as vascular remodelling, which are all involved in the regulation of arterial blood pressure. Thus leptin and the RAS may act together in the pathogenesis of essential hypertension. The present study aimed to answer the following question: does an interrelationship exist between leptinaemia and the plasma renin activity (PRA) profile in normotensive and hypertensive subjects? Forty-three patients with essential hypertension (EHP) (23 females, 20 males, mean age 39.0 +/- 1.8 years, mean body mass index (BMI) 26. 8 +/- 0.6 kg/m2, mean arterial pressure (MAP) 123 +/- 2 mm Hg) and 32 healthy subjects (NTS) (18 females, 14 males, mean age 38.6 +/- 2. 2 years, mean BMI 25.4 +/- 0.5 kg/m2, MAP 95 +/- 1 mm Hg) were examined. Plasma leptin levels were estimated once after the administration of a diet containing 100-120 mmol Na/day and after overnight 8-h recumbency. PRA was estimated twice: first after the administration of a diet containing 100-120 mmol Na day and overnight 8-h recumbency (PRA I), and a second time after 3 days of sodium restriction (20 mmol Na/day), and 3 h of upright position (PRA II). Antihypertensive drugs were withdrawn 7 days before the study. In EHP plasma leptin concentration was insignificantly higher than in NTS (14.0 +/- 2.0 vs10.8 +/- 1.5 ng/ml respectively). Only females with hypertension showed a significant positive correlation between plasma leptin concentrations (expressed as the logarithmic values) and PRA I. Using the multiple regression analysis, in all studied subjects (EHP and NTS together), logarithm (log) of plasma leptin concentrations was significantly related to gender, BMI and MAP. Multiple regression analysis performed separately for EHP or NTS revealed a significant relation of log plasma leptin concentrations with gender and BMI. A significant correlation was found between log leptinaemia values and BMI, mean and systolic blood pressure respectively if the whole group of subjects (EHP+NTS) or EHP and NTS separately were analysed. Especially in hypertensive women a highly significant correlation was found between log plasma leptin concentrations and MAP. We conclude that a significant relationship between leptinaemia and PRA does exist in females with EH and that participation of both PRA and leptin in the pathogenesis of EH in females seems to be likely.
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PMID:Relationship between plasma renin profile and leptinaemia in patients with essential hypertension. 1096 18

Recent studies have shown that tumor necrosis factor-alpha (TNFalpha), secreted by macrophage, adipocyte and muscle cells, are associated with insulin resistance syndrome i.e., hyperinsulinemia, hypertriglyceridemia and decreased high density lipoprotein (HDL) cholesterol levels. However, it is unclear whether plasma TNFalpha levels relate to insulin resistance syndrome in subjects with essential hypertension who are also characterized by an insulin resistance state. We recruited 85 nondiabetic subjects (45 men and 40 women) with essential hypertension and 85 nondiabetic subjects who were matched for age, sex and body mass index (BMI) to determine their fasting plasma glucose, insulin and lipoprotein concentrations, their glucose and insulin responses to an oral glucose challenge, and their degrees of insulin resistance. Fasting plasma leptin and TNFalpha levels were measured by radioimmunoassay and chemiluminescent enzyme immunometric assay respectively. Total body fat mass was assessed by the bioelectrical impedance method. The results showed that fasting plasma leptin levels were similar between hypertensive and normotensive subjects (7.9 +/- 0.6 vs 7.4 +/- 0.7 ng/ml, p=0.190). Fasting plasma TNFalpha concentrations were not different between subjects with hypertension and normotension (10.5 +/- 0.5 vs 9.8 +/- 0.4 pg/ml, p=0.360). Fasting plasma TNFalpha concentrations were not different across three subgroups of the insulin resistance both in hypertensive patients (8.4 +/- 0.4 vs. 10.9 +/- 1.6 vs. 9.9 +/- 1.0 pg/ml, p=0.297) and normotensive subjects (9.2 +/- 0.7 vs. 9.3 +/- 0.9 vs. 9.7 +/- 0.9 pg/ml, p=0.875). Fasting plasma TNFalpha values showed significantly positive correlations with triglyceride concentrations (p<0.03) but negative correlation with HDL cholesterol concentrations (p<0.04) in normotensive but not in hypertensive individuals. These relations persisted even after adjustment for BMI and total fat mass. In conclusion, our data indicated that circulating levels of TNFalpha did not differ between hypertensive subjects and normotensive controls. Plasma TNFalpha concentrations correlated positively with fasting plasma triglyceride levels and negatively with HDL cholesterol concentrations in normotensive but not in hypertensive subjects. The influence of TNFalpha on carbohydrate and lipoprotein metabolism in hypertensive patients deserves further investigations.
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PMID:Plasma tumor necrosis factor alpha levels and insulin sensitivity in hypertensive subjects. 1097 64

Recent animal studies indicate that leptin is involved in the regulation of blood pressure through the leptin receptor. Therefore, 51-yr-old men (N = 284) were selected; and anthropometric, endocrine, metabolic, and hemodynamic variables were examined in relation to polymorphisms of the leptin receptor gene (LEPR), by restriction fragment length polymorphism technique. Three polymorphisms were examined: Lys109Arg in exon 4, Gln223Arg in exon 6, and Lys656Asn in exon 14. In comparison with Lys109 homozygotes, Arg109 homozygotes (9%) showed lower body mass index (BMI) and abdominal sagittal diameter, as well as lower systolic (10.0 mm Hg) and diastolic (7.8 mm Hg) blood pressure. Additionally, Arg223 homozygotes (26.8%) showed lower blood pressure (7.6/5.7 mm Hg) than Gln223 homozygotes. These lower blood pressure levels were independent of other variables. No differences were found with the Lys656Asn polymorphism. Measurements of body fat mass correlated with leptin concentration in Lys109 homozygotes and in Lys109 heterozygotes but not in Arg109 homozygotes. Blood pressure correlated with leptin only in men carrying the wild-type allele Lys109. With both elevated BMI and leptin, Lys109 homozygotes had higher blood pressure than the Arg109 homozygous men (12.4/6.9 mm Hg). Men with blood pressure > or = 140/90 mm Hg had, in comparison with normotensive men, increased BMI and leptin levels, and Lys109 homozygotes were significantly more prevalent. These results suggest that leptin is associated with blood pressure regulation in men through the leptin receptor. When BMI and leptin are elevated, increased blood pressure is found only with the most prevalent LEPR genotype at codons 109 and 223, whereas variants of this receptor seem to protect from hypertension. This might explain why not all obese men are hypertensive.
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PMID:Hypertension in obesity and the leptin receptor gene locus. 1099 97


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