Pulsed processing by cold plasma, applied to industrial emission control.

A promising pollution control technology is cold plasma driven chemical processing. The plasma is a pulsed electric gas discharge inside a near atmospheric-pressure-temperature reactor. The system is energized by a continuous stream of very short high-voltage pulses. The exhaust gas to be treated flows through the reactor. The methods applied involve the development of robust cold plasma systems, industrial applications and measuring technologies. Tests of the systems were performed at many industrial sites and involved control of airborne VOC (volatile organic compound) and odor. Electrical, chemical and odor measuring data were collected with state-of-the-art methods. To explain the test data an approximate solution of global reaction kinetics of pulsed plasma chemistry was developed. It involves the Lambert function and, for convenience, a simple approximation of it. The latter shows that the amount of removal, in good approximation, is a function of a single variable. This variable is electric plasma power divided by gas flow divided by input concentration. In the results sections we show that in some cases up to 99% of volatile pollution can be removed at an acceptable energy requirement. In the final sections we look into future efficiency enhancements by implementation of (sub)nanosecond pulsed plasma and solid state high-voltage technology and by integration with catalyst technology.

[Bronchus insufficiency: prevention and therapy]. / Bronchusinsuffizienz: Prävention und Therapie.

In order to achieve respectable postoperative outcomes after lung resection it is essential to understand the mechanism of bronchus healing. The bronchus seal should be air-tight and consist of monofilament suture or staples. The bronchus suture should be covered with vital tissue (lung, mediastinum, muscle flap). A complication in the process of bronchus healing should be diagnosed as early as possible in order to stop the destructive effect of the infection as rapidly as possible.

[Influence of nosocomial infections on resection of tracheal stenosis after tracheotomy]. / Bedeutung nosokomialer Infektionen bei derResektion trachealer Stenosen nach Tracheotomie.

BACKGROUND: Complications located at the tracheostoma often occur in combination with nosocomial infections. We posed the question: how is the surgical result in tracheal resections influenced by bacterial contamination with multiresistant germs? PATIENTS AND METHODS: Between 2005 and 2009 we performed a primary end-to-end-resection of the trachea after tracheotomy in 30 patients. The demographic basic data, the diagnostic data on tracheal stenosis after decanullation and type of tracheotomy were documented. Preoperatively all patients underwent a flexible bronchoscopy with bronchial lavage. All patients received an antibiotic inhalation therapy postoperatively. RESULTS: 16 patients presented a status post-permanent tracheotomy (PT), in 14 cases after percutaneous dilatative tracheotomy (PDT). In 64 % of all cases the preoperative bronchial lavage was positive for bacterial contamination. The major pathogen was with 23 % a multiresistant Pseudomonas aeruginosa (MR). In three cases long-term-complications occurred, all of which were bacterially contaminated. CONCLUSION: After long-term intubation a bacterial contamination is very common and presents a negative predictor for the outcome of primary tracheal end-to-end resections. A prophylactic postoperative antibiotic therapy can improve the short- and long-term results.

Operational point of neural cardiovascular regulation in humans up to 6 months in space.

Entering weightlessness affects central circulation in humans by enhancing venous return and cardiac output. We tested whether the operational point of neural cardiovascular regulation in space sets accordingly to adopt a level close to that found in the ground-based horizontal position. Heart rate (HR), finger blood and brachial blood pressure (BP), and respiratory frequency were collected in 11 astronauts from nine space missions. Recordings were made in supine and standing positions at least 10 days before launch and during spaceflight (days 5-19, 45-67, 77-116, 146-180). Cross-correlation analyses of HR and systolic BP were used to measure three complementary aspects of cardiac baroreflex modulation: 1) baroreflex sensitivity, 2) number of effective baroreflex estimates, and 3) baroreflex time delay. A fixed breathing protocol was performed to measure respiratory sinus arrhythmia and low-frequency power of systolic BP variability. We found that HR and mean arterial pressure did not differ from preflight supine values for up to 6 mo in space. Respiration frequency tended to decrease during prolonged spaceflight. Concerning neural markers of cardiovascular regulation, we observed in-flight adaptations toward homeostatic conditions similar to those found in the ground-based supine position. Surprisingly, this was not the case for baroreflex time delay distribution, which had somewhat longer latencies in space. Except for this finding, our results confirm that the operational point of neural cardiovascular regulation in space sets to a level close to that of an Earth-based supine position. This adaptation level suggests that circulation is chronically relaxed for at least 6 mo in space.

[Pulmonary nodules in underlying malignant diseases--not necessarily metastases of the primary tumour]. / Der pulmonale Rundherd bei maligner Grunderkrankung--nicht zwingend eine Metastase des Primärtumors.

BACKGROUND: In this study the histological examination of pulmonary nodules and a comparison of the number of pre-, intra- and post-operative lung metastases in patients with a previous history of malignant disease were assessed. PATIENTS AND METHODS: Between 1998 and 2003 we operated on 276 patients with suspected lung metastases. The histology of the primary tumour, the number of preoperatively diagnosed nodules, the number of lesions removed during surgery and the number of histologically confirmed metastases of 276 patients are presented. RESULTS: In 276 patients a resection was performed. 161 of the patients were men (58.1%). The median age was 62 years (range: 21-86 years). In 110 cases a left-sided thoracotomy was performed (39.8%), in another 110 cases a right-sided thoracotomy was performed and in 56 cases we performed a bilateral thoracotomy (20.4%). In 15.2% the histology of the resected nodules was benign. In 8.6% of the cases the histological examination showed a primary lung cancer in stage I, in 74.4% of the cases the histology confirmed a metastasis of the primary cancer. CONCLUSIONS: Solitary pulmonary nodules in patients with a previous history of malignant disease should always be resected for histological examination. Multiple pulmonary nodules should be histologically reappraised if there is any doubt about the entity.

Estimating the direct impact of new conjugate vaccines against invasive pneumococcal disease.

New pneumococcal conjugate vaccines (PCVs) are now becoming available. These formulations differ from the heptavalent diphtheria toxin variant conjugate vaccine (7vCRM, Prevenar/Prevnar) both in the number of serotypes and in serotype-specific immunogenicity. This review proposes an algorithm that attempts to predict the overall impact of these differences in vaccine formulation and immunogenicity on invasive pneumococcal disease (IPD) effectiveness. It builds on the principles underlying WHO licensure criteria for new PCVs, that serotype-specific anti-polysaccharide immunogenicity is potentially predictive of effectiveness. The algorithm used three sources of information: serotype-specific effectiveness data for 7vCRM, serotype-specific head-to-head immunogenicity data with 7vCRM and a recently licensed 10-valent pneumococcal non-typeable H. influenzae protein D-conjugate vaccine (PHiD-CV, Synflorix), and epidemiological information regarding the serotypes causing IPD in young children. Based on this algorithm, PHiD-CV and 7vCRM are predicted to prevent approximately 60-80% and 45-80%, respectively of IPD in young children worldwide, with significant variability by country and region.

Effect of 35 years beta-adrenergic blockade therapy on autonomic cardiovascular modulation. A case study.

The influence of long duration beta-blockade on autonomic and cardiovascular function remains not completely understood. The aim of this study was to evaluate the effect of long duration beta-adrenergic blockade treatment for hypertension control, on autonomic cardiovascular control in a 78-year-old male patient in relation to population findings. Heart rate variability was determined in the frequency domain (Total power, low frequency power and high frequency power), during baseline (supine and standing) and during 24 hour Holter recording. Results were compared with heart rate and heart rate variability data obtained from a normal healthy male population as a function of age. Circadian rhythm remained present. Heart rate during daytime was lower compared to the population group. None of the heart rate variability parameters were different from the normal population age group. Our results show that after 35 years of beta-blockade treatment, autonomic modulation of cardiac function remains within normal limits for that age group. Blood pressure remained at the higher limits (120-150/60-80 mmHg), but under control.

Respiratory modulation of cardiovascular rhythms before and after short-duration human spaceflight.

AIM: Astronauts commonly return from space with altered short-term cardiovascular dynamics and blunted baroreflex sensitivity. Although many studies have addressed this issue, post-flight effects on the dynamic circulatory control remain incompletely understood. It is not clear how long the cardiovascular system needs to recover from spaceflight as most post-flight investigations only extended between a few days and 2 weeks. METHODS: In this study, we examined the effect of short-duration spaceflight (1-2 weeks) on respiratory-mediated cardiovascular rhythms in five cosmonauts. Two paced-breathing protocols at 6 and 12 breaths min(-1) were performed in the standing and supine positions before spaceflight, and after 1 and 25 days upon return. Dynamic baroreflex function was evaluated by transfer function analysis between systolic pressure and the RR intervals. RESULTS: Post-flight orthostatic blood pressure control was preserved in all cosmonauts. In the standing position after spaceflight there was an increase in heart rate (HR) of approx. 20 beats min(-1) or more. Averaged for all five cosmonauts, respiratory sinus dysrhythmia and transfer gain reduced to 40% the day after landing, and had returned to pre-flight levels after 25 days. Low-frequency gain decreased from 6.6 (3.4) [mean (SD)] pre-flight to 3.9 (1.6) post-flight and returned to 5.7 (1.3) ms mmHg(-1) after 25 days upon return to Earth. Unlike alterations in the modulation of HR, blood pressure dynamics were not significantly different between pre- and post-flight sessions. CONCLUSION: Our results indicate that short-duration spaceflight reduces respiratory modulation of HR and decreases cardiac baroreflex gain without affecting post-flight arterial blood pressure dynamics. Altered respiratory modulation of human autonomic rhythms does not persist until 25 days upon return to Earth.

Influence of supplemental magnesium, tryptophan, vitamin C, and vitamin E on stress responses of pigs to vibration.

Our objectives were to investigate and compare the effects of supplemental Mg, Trp, vitamin E (vit E), and vitamin C (vit C) on stress responses of pigs undergoing transport simulation. In this study, 126 pigs (25.1 +/- 4.4 kg BW) were allocated to one of the six following treatments: 1) negative control (no supplementation); 2) positive control (i.m. injection with 0.5 mg of carazolol/20 kg BW 12 h before vibration, beta-blocker); 3) Trp (additional amount of 6 g/kg of feed for 5 d, as-fed basis); 4) Mg (3 g/L drinking water for 2 d); 5) vit E (additional amount of 150 mg/kg of feed for 21 d, as-fed basis); 6) or vit C (additional amount of 300 mg/kg of feed for 21 d, as-fed basis). Pigs were treated in groups of three, and each treatment was replicated seven times. Feed and water intake were not different among treatments. Heart rate variables (mean, peak, and minimum heart rate, ventricular ectopic beats, and ST elevation of Channels A and B) and heart rate variability were registered from the night before vibration. Pigs were subjected to vibration in a transport simulator (8 Hz, 3 m/s) for 2 h and allowed to recover for 2 h. Generally, the positive control pigs had the lowest heart rate values (mean, peak, minimum heart rate, ST elevation of Channel A; P < 0.05), whereas Mg and Trp decreased ventricular ectopic beats and ST elevation of Channel B, respectively. The effect of vit C and E as vagal stimulators was clearly visible, whereas carazolol and Mg clearly blocked the sympathetic pathways of the autonomic nervous system. During vibration, the negative control pigs lay the least, and Mg pigs the most (P < 0.05). Salivary cortisol concentrations (taken before and after vibration and after recovery) showed that vit E pigs produced the least cortisol during stress periods. Intermediary metabolites (glucose, lactate, creatine kinase, and NEFA) were analyzed in plasma from blood taken before and after vibration. At the two sampling points, the vit E and Mg pigs had the lowest NEFA concentrations (P < 0.05), and the vit E pigs also had the lowest lactate concentrations before vibration. Urine samples were collected before and after vibration to determine catecholamine concentrations; only negative control pigs had an increase (P = 0.04) in epinephrine concentration, despite large individual variation. In general, these results indicate that the supplementation of Trp, Mg, vit E, or vit C improved coping ability of pigs during vibration comparison with the negative control treatment. A muscular injection of carazolol influenced only the heart rate variables.

Feasibility of a quality assurance programme of bedside blood glucose testing in a hospital setting: 7 years' experience.

AIMS: Description of the long-term use of a quality assurance (QA) programme for bedside capillary blood glucose (CBG) testing in a general hospital. METHODS: The main points of the programme were selection of instrumentation using a standardized testing procedure, design and implementation of a quality control (QC) procedure, and training and motivation of nurses. The QC procedures consisted of a daily aqueous control and a weekly split-sample control (a measurement on a capillary blood sample using the glucose meter and on a simultaneously drawn venous sample with the laboratory analyser). When the result was out of range, a laboratory technician visited the ward to investigate the problem. All wards received a weekly report. RESULTS: The programme was introduced in 1995 and followed up through 2002. The split-sample control was more efficient in detecting clinically relevant errors than the aqueous control. Most errors (91-97%) were operator-related rather than instrument-related. The compliance with the split-sample controls remained high, with 84-91% of weekly controls performed over 7 years. Respectively 91, 95 and 96% of the measurements remained within the range of +/- 20% of the laboratory value in the years 2000, 2001 and 2002. CONCLUSION: A QA programme of bedside CBG testing can successfully be implemented. It is feasible to obtain a satisfying level of measurement accuracy and to maintain a high level of compliance with the programme over several years. Split-sample controls are an essential part of the control procedure.

Parasympathetic heart rate modulation during parabolic flights.

During parabolic flight short periods of microgravity and hypergravity are created. These changes influence cardiovascular function differently according to posture. During the 29th parabolic flight campaign of the European Space Agency (ESA), the electrocardiogram (ECG) was recorded continuously in seven healthy volunteers in two positions (standing and supine). Five different phases were differentiated: 1 g (1 g=9.81 m/s(2)) before and after each parabola, 1.8 g at the ascending leg of the parabola (hypergravity), 0 g at the apex, 1.6 g at the descending leg (hypergravity). We assessed heart rate variability (HRV) by indices of temporal analysis [mean RR interval (meanRR), the standard deviation of the intervals (SDRR), and the square root of the mean squared differences of successive intervals (rMSSD) and coefficient of variation (CV)]. In the supine position no significant differences were shown between different gravity phases for all HRV indices. In the standing position the 0 g phase showed a tendency towards higher values of meanRR compared to the control and to the other phases ( p=NS). SDRR, rMSSD and CV were significantly higher compared to control ( p<0.05). Significantly higher values for meanRR in the supine position at 1 g and hypergravity ( p<0.05) were found when compared to standing. SDRR was significantly higher at 0 g in the standing position compared to supine [95 (44) ms vs. 50 (15) ms; p<0.05] and lower in other phases. rMSSD and CV showed the same trend ( p=NS). We confirm that, during parabolic flights, position matters for cardiovascular measurements. Time domain indices of HRV during different gravity phases showed: (1) higher vagal modulation of the autonomic nervous system in microgravity, when compared with normo- or hypergravity in standing subjects; and (2) no differences in supine subjects between different g phases.

Effects of melanocortins on cardiovascular regulation in rats.

1. Of the melanocortin peptides, gamma(2)-melanocyte-stimulating hormone (MSH) has been attributed a cardiovascular effect, inducing an increase in blood pressure and heart rate. Although still controversial, this effect, based on pharmacological blockade experiments, is supposed to be mediated through sympathetic activation. 2. The aims of the present study were to identify the N-terminal pro-opiomelanocortin (N-POMC) fragments and melanocortins that influence blood pressure and heart rate and to investigate the real-time changes in baroreflex sensitivity and in sympathetic and vagal modulation underlying cardiovascular effects in conscious rats without the use of pharmacological blockade. 3. Intracerebroventricular administration of different melanocortins and N-POMC induced a long-lasting dose- dependent pressor response from 1 nmol onwards, with only a small initial bradycardic response with the highest dose. 4. Coinciding with this pressor response, an elicitation of the low-frequency (LF) component was observed in spectral analysis of both blood pressure variability (BPV) and heart rate variability (HRV), followed by the high-frequency (HF) component in at least BPV. Baroreflex sensitivity remained unchanged. 5. After intravenous administration, gamma(2)-MSH produced a short-lasting dose-dependent pressor and cardioaccelerator response with very rapid onset with concentrations from 1 nmol onwards. 6. Continuous infusion of gamma(2)-MSH depressed baroreflex sensitivity and simultaneously increased both components of BPV, with a radical reduction of the LF component and a preserved vagal HF component in HRV. 7. Of all the intravenously administered melanocortins, only gamma(2)-MSH was active. The central effect is likely to depend on an increase of (alpha-)sympathetic outflow. 8. For the peripheral effect, gamma(2)-MSH appeared to act as a baroreceptor reflex-blocking agent, being compatible with a role in the acute stress response.

Head out of water immersion as simulation study: an heart rate variability study.

During head out of water immersion (HOI), the hydrostatic pressure on the tissues of the lower limbs causes an increase in thoracic blood volume and a high vascular perfusion. This blood shift results in changes in autonomic balance. The aim of this study was to evaluate the activity of the autonomic nervous system, as obtained from the analysis of heart rate variability (HRV), during HOI at 2 different temperatures and compare these results with data obtained during parabolic flight. In HOI, two different positions (sitting and standing) were compared. Results showed a shift to vagal activity as well during HOI as in microgravity during parabolic flight.

Heart rate variability during gravity transitions.

During parabolic flight short periods of microgravity and hypergravity are created. During standing position time domain analysis showed higher vagal modulation of the autonomic nervous system in microgravity compared to hypergravity. We hypothesised that this behaviour could better be unravelled by analysis of frequency domain heart rate variability (HRV) techniques. During parabolic flights a subject is exposed to 20-25 sec periods of microgravity (at the top of the parabola), preceded and followed by 20 sec duration episodes of hypergravity. No significant differences were found in the frequency parameters in supine position for each of the phases. In standing position higher values for Total Power, high frequency (HF), low frequency (LF), LF/HF and HF% in 0 g phase were found in comparison with the 3 other phases. LF% was significant lower in standing position at 0 g compared with 1.8 g. These results show that despite the time window limitations, frequency analysis is still possible on ultra short data segments.

Wavelet decomposition analysis of heart rate variability in aerobic athletes.

Heart rate variability (HRV) can be quantified, among others, in the frequency domain using digital signal processing (DSP) techniques. The wavelet transform is an alternative tool for the analysis of non-stationary signals. The implementation of perfect reconstruction digital filter banks leads to multi resolution wavelet analysis. Software was developed in LabVIEW. In this study, the average power was compared at each decomposition level of a tachogram, containing the consecutive RR-intervals of two groups of subjects: aerobic athletes and a control group. Compared to the controls, the aerobic athletes showed an increased power in all frequency bands. These results are in accordance with values obtained by spectral analysis using the Fourier transform, suggesting that wavelet analysis could be an appropriate tool to evaluate oscillating components in HRV, but in addition to classic methods, it also gives a time resolution.

Analysis of heart rate variability with correlation dimension method in a normal population and in heart transplant patients.

INTRODUCTION: The correlation dimension (CD) method is related to chaos theory and is used to quantify heart rate variability (HRV). The CD is a measure for the amount of correlations present in the signal. METHODS: The algorithm used to calculate the CD is based on the method of Grassberger and Proccacia. The method was first validated on signals with known CD and then applied to HRV-signals of heart transplants and an age-matched control group of healthy subjects. The CD of the corresponding surrogate time series was calculated to investigate non-linear correlations in the HRV-signal. Circadian variations of the CD were studied in 20 healthy subjects, including men and women. RESULTS: The value of the CD for healthy subjects ranged from 2.12 to 5.53 with a mean value of 4.32. For heart transplants, only a few time series showed a finite value of the CD that varied between 2.10 and 5.60. Also, a significant difference was found between the CD of the original and the surrogate time series in healthy subjects. The CD of women is higher than the CD of men, and this difference was more pronounced during the night than during the day. CONCLUSIONS: This limited study shows that the CD alone cannot be used to make a distinction between HRV-signals of healthy subjects and of heart transplants. However, there is evidence that there are non-linear correlations present in the HRV-signal and that there are significant gender and circadian differences in the CD.

Short-term heart rate variability in young athletes.

OBJECTIVES: The purpose of this study was to determine whether the type of training in a young population differentiates heart rate variability parameters between athlete groups and sedentary subjects. METHODS: The effect of different types of physical training on heart rate variability was evaluated in 10 aerobic trained athletes, in 7 anaerobic trained athletes, in 7 rugby players (mixed type training) and in 10 sedentary control subjects. All groups were age matched (18-34 years). Electrocardiogram tracings were recorded digitally in the supine position and standing position. Measures of heart rate variability were obtained, from both time- and frequency analysis of 10 min resting heart rate. After these tests, blood pressure was measured using an automatic inflation cuff. RESULTS: Resting heart rate was lower in aerobic and mixed type athletes compared to controls. Only aerobic athletes had evidence of increased vagal activity in the time domain compared with control subjects (increased SDNN supine, increased rMSSD supine and standing and pNN50 standing). In the frequency domain, aerobic athletes presented with both higher low-frequency and high-frequency power in the standing position and low-frequency power in the supine position compared to controls. CONCLUSIONS: It can be concluded that heart rate variability is affected by chronic exercise, especially in endurance trained athletes. This infers that especially aerobic exercising can have beneficial effects on the cardiovascular risk profile.

The analysis of heart rate variability in unrestrained rats. Validation of method and results.

An experimental setting and software were developed to evaluate cardiac autonomic function in unrestrained rats. Subcutaneously implanted ECG electrodes and an indwelling venous catheter were tunneled to a tail cuff in five rats. The ECG was A/D converted at 1000 Hz. After peak detection, a time series of RR intervals was obtained. Programs for the analysis of heart rate variability (HRV) were implemented in LabVIEW. Statistical properties were determined in the time domain. After cubic spline function curve fitting, resampling at 0.1 s and test for stationarity, power spectral analysis was performed on sampled records of 30 min duration after applying a sliding Hanning window (Welch method: 256 points (duration 25.6 s), 50% overlap and 0.039 Hz resolution). Algorithms were tested with simulated signals consisting of isolated frequency components, which were retrieved at their exact locations. Physiological validation of the system was performed by, beta-adrenergic and cholinergic blockade and by forced breathing at a fixed rate. Measurements were performed on five unrestrained rats under basal conditions. Mean RR was 174.2 +/- 3.6 ms; S.D., 13.3 +/- 4.6 ms; rMSSD, 5.2 + /- 1.2 ms; pNN10, 3.5 +/- 1.9% and pNN5, 18.7 +/- 6.4%. Low (0.19-0.74 Hz) and high frequency (0.78-2.5 Hz) power were determined (and also percent of low to total and high to total): 18.42 +/- 10.74 ms2 (22.9 +/- 6.5%) and 15.66 +/- 5.56 ms2 (19.9 +/- 2.7%), and the ratio low/high: 1.16 +/- 0.39. In conclusion, HRV analysis programs were developed and thoroughly tested through simulations and in vivo, under basal conditions and after pharmacological blockades. Using this software, HRV data from unrestrained rats were obtained.

Zinc regulation of insulin-like growth factor-I (IGF-I), growth hormone receptor (GHR) and binding protein (GHBP) gene expression in rat cultured hepatocytes.

Dietary zinc depletion in vivo attenuates growth, decreases circulating insulin-like growth factor-I (IGF-I) and liver growth hormone (GH) receptors (GHR). In order to investigate a direct role of zinc in the regulation of IGF-I, GHR and GH binding protein (GHBP) gene expression, we evaluated the response of their mRNAs to changes in zinc availability in primary culture of rat hepatocytes. Exposition of cells to the zinc chelator DTPA (diethylenetriaminepenta-acetic acid) did not decrease IGF-I and GHBP mRNAs while it strongly inhibited metallothionein (MT) gene expression. On the other hand, zinc excess (50 vs. 1.5 microM) decreased IGF-I, GHR and GHBP mRNAs while it stimulated MT mRNA. However, the response of IGF-I to GH was not affected by the exposure to DTPA nor zinc excess. Furthermore, zinc repletion of primary cultured hepatocytes isolated from zinc-deprived rats did not increase IGF-I nor GHR/GHBP mRNAs. Therefore, our results suggest that the IGF-I decline induced in vivo by zinc deficiency is not caused by reduced extracellular zinc availability at the hepatocyte level. Although IGF-I and MT gene expression is down-regulated by dietary zinc depletion, underlying mechanisms of regulation are different for both genes.

Estrogen modulates AT1 receptor gene expression in vitro and in vivo.

BACKGROUND: The AT1 receptor has been implicated in the pathogenesis of hypertension and atherosclerosis. Estrogen deficiency is also associated with cardiovascular diseases. Therefore, we examined the AT1 receptor gene expression in ovariectomized rats with and without estrogen replacement therapy and the influence of estrogen on AT1 receptor expression in cultured vascular smooth muscle cells. METHODS AND RESULTS: Rat aortic tissue was examined 5 weeks after ovariectomy. In one group, estrogen (1.7 mg estradiol) was administered during the 5-week period. Functional experiments assessed angiotensin II-induced contraction of aortic rings. AT1 receptor mRNA levels were measured by quantitative polymerase chain reaction and Northern blotting. AT1 receptor density was assessed by radioligand binding assays. These techniques were also applied in cultured vascular smooth muscle cells. The efficacy of angiotensin II on vasoconstriction was significantly increased in aortas from ovariectomized rats. As assessed by radioligand binding assays, AT1 receptor density was increased to 160% without changes in receptor affinity during estrogen deficiency. AT1 receptor mRNA levels were consistently increased to 187% in ovariectomized rats compared with sham-operated animals. Estrogen substitution therapy in ovariectomized rats reversed this AT1 receptor overexpression. To explore the underlying mechanisms, the direct influence of estradiol on AT1 receptor expression was investigated in VSMCs. Estradiol (1 micromol/L) led to a time-dependent downregulation of AT1 receptor mRNA, with a maximum of 33.3% at 12 hours. There was a correlative decrease in AT1 receptor density. CONCLUSIONS: This novel observation of estrogen-induced downregulation of AT1 receptor expression could explain the association of estrogen deficiency with hypertension and atherosclerosis, because activation of the AT1 receptor plays a key role in the regulation of blood pressure, fluid homeostasis, and vascular cell growth.