Twenty-four-hour ambulatory blood pressure measurements (ABPM) are likely to eliminate the stress of visits and observer bias in office blood pressure (BP) recordings, allow consideration of the circadian variability in BP, and correlate well with target organ damage. To define the prevalence of "white coat" hypertension in a rural community to a nonacademic setting, and to assess age and sex related differences, we studied 131 patients who had more than two prior office diastolic BP measurements greater than 90 mm Hg and less than 115 mm Hg. Blood pressure was measured every 10 to 60 min for 24 h using the SpaceLabs 90207 device. Office BP readings were higher than ABPM in the group as a whole, in individual age groups, and in both sexes. The differences were more pronounced at night. Average differences between office and ambulatory BP ranged between 14.4 +/- 1.7/2.9 +/- 2.0 (ABPM at 10:00), and 33.8 +/- 2.3/22.8 +/- 1.5 mm Hg (systolic/diastolic +/- SE) (ABPM at 01:00). The nighttime drop in systolic BP was not apparent in subjects more than 65 years old. Women had a proportionately higher mean office BP than men (115.0 +/- 0.9 office v 110.2 +/- 1.3 mm Hg ABPM in women and 112.3 +/- 0.9 v 104.3 +/- 1.1 mm Hg in men) (P = .013), and the elderly did not display the relationship between ambulatory and office mean BP seen in younger subjects (r = 0.15, P = .30 v r = 0.36, P = .0004, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Gonadotropin-releasing hormone (GnRH) and gonadal steroids regulate synthesis and release of luteinizing hormone (LH). GnRH is secreted intermittently by the hypothalamus, producing pulsatile LH release, and a pulsatile GnRH stimulus is required to maintain LH secretion. We report the regulatory effects of GnRH Recently, cDNAs coding for LH a and /3 subunits were isolated (16,17), and we have used these cDNAs as hybridization probes to develop a sensitive assay for mRNAs using dot-blot hybridization of extracted cytoplasmic RNA from rat pituitaries.We employed this mRNA quantitation assay to study the effects of GnRH pulse injections on expression of the genes for LH a and p subunits in gonadectomized male rats that were given testosterone implants. In this animal model endogenous GnRH secretion is markedly reduced, as judged by infrequent serum LH pulses (18). Thus assessment of the effects of exogenous GnRH pulse injections, given to mimic the intermittent physiologic stimulus, is not unduly complicated by endogenous GnRH secretion. In addition, experiments are performed in the presence of stable physiologic concentrations of testosterone, which avoids the potential effects of fluctuating serum testosterone levels in intact animals (19). This model has been previously used to study the effects of testosterone in regulating GfiRH receptor and gonadotropin responses to a pulsatile GnRH stimulus (19). In the present study we examined the effects of different doses of GnRH per pulse injection on GnRH membrane receptors and LH subunit gene expression to assess their role in the regulation of gonadotropin secretion. MATERIALS AND METHODSMale Sprague-Dawley rats (250-300 g) were castrated and implanted with two 20-mm Silastic implants containing testosterone, to produce a serum testosterone concentration of 2.3 ± 0.12 ng/ml (mean ± SEM). Beginning immediately after recovery from anesthesia, GnRH pulse (10-250 ng per pulse) or control saline injections were given every 30 min for 48 For mRNA quantification pituitaries were individually homogenized in 10 mM Tris/0.5% Nonidet P-40/1 mM EI)TA, pH 7.4, and the homogenate was centrifuged (13,000x g for 5 mmin). DNA was measured (20) in the nuclear pellet, and total RNA was extracted from the cytosol supernatant by using a phenol/chloroform/isoamyl alcohol mixture (100:100:1, Abbreviations: GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone. §To whom reprint requests should be addressed
The pattern of pulsatile GnRH secretion is abnormal in some women with hypothalamic amenorrhea (HA) consequent to previous exercise or weight loss. Both diminished frequency pulsatile LH secretion, and by inference GnRH secretion, and normal LH pulsatility have been reported. We assessed whether the patterns of GnRH secretion varied with time by measuring plasma LH every 15 or 20 min for 24 h on 1-3 occasions during a 10-month period in 14 women with HA (a total of 24 studies). During the day, mean LH pulse frequency [1.0 +/- 0.1 (+/- SE) pulses/8 h] was lower than that in normal women in the early follicular phase of their cycles (5.1 +/- 0.6), and the frequency in individual HA patients was lower than early follicular phase values in 16 of 17 studies. The slow daytime LH pulse frequency also was a consistent finding, in that the values in repeat studies varied by less than 2 pulses/8 h in all but 1 patient. LH pulse frequency (2.0 +/- 0.4 pulses/8 h) was higher and more variable during sleep, and normal early follicular phase frequencies were found in 20% of patients with HA. The mechanisms whereby GnRH pulse frequency is reduced are not known. alpha-Adrenergic agonist drugs stimulate GnRH pulsatile secretion in rodents, but administration of the alpha 2-agonist clonidine (0.15 mg, orally, at 0800 and 2000 h) did not increase the frequency of LH pulses in 7 women (1.7 +/- 0.4 pulses/8 h). In contrast, administration of naloxone (1 mg/m2 X h, iv) for 8 h during the day to 14 patients, increased LH pulse frequency (3.3 +/- 0.5 pulses/8 h). In 8 of these 14 women, LH pulse frequency (4.9 +/- 0.4 pulses/8 h) increased into the range found during the normal early follicular phase, while in the other 6 women pulse frequency was not significantly increased (1.4 +/- 0.4 pulses/8 h). Plasma estradiol levels were similar in naloxone-responsive and unresponsive women, but spontaneous LH pulse frequency was higher at night in naloxone-responsive patients (2.9 +/- 0.6 vs. 1.4 +/- 0.3 pulses/8 h). The presence of nocturnal LH pulses did not predict responsiveness to naloxone, however, and LH pulse frequency was less than 2 pulses/8 h in 4 of the women who responded to naloxone. These data indicate that slow frequency GnRH secretion is a common finding during the day in women with HA. GnRH secretion is more variable at night, suggesting that the mechanisms involved in reducing pulsatile GnRH secretion are less effective during sleep.(ABSTRACT TRUNCATED AT 400 WORDS)
To test the hypothesis that androgens may play a role in the pathogenesis of atherosclerosis and hypertension, we investigated the association of delta 5 dehydroepiandrosterone sulfate [DHEAS]) and delta 4 (free testosterone [FT]) androgens with the resting, seated blood pressure (BP) levels and cardiovascular risk factors in 280 young, healthy women 18 to 24 years of age. After application of multiple regression analysis, systolic BP was positively and independently correlated with the ratio of dehydroepiandrosterone sulfate to free testosterone (DHEAS/FT), fasting insulin levels, and the diastolic BP with DHEAS/FT only. The DHEAS/FT ratio proved to be a stronger predictor of the BP levels than either hormone alone. Further, uric acid concentrations and HDL/total cholesterol ratio were independently correlated with both FT and body mass index in these young women. Serum triglycerides were independently correlated with FT and central body fat distribution. These data suggest that serum androgen concentrations are important independent predictors of cardiovascular risk factors and that the ratio of dehydroepiandrosterone sulfate to free testosterone ratio is an independent predictor of blood pressure levels in young women.
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