Closed DHS system to prevent dissolved methane emissions as greenhouse gas in anaerobic wastewater treatment by its recovery and biological oxidation.

Anaerobic wastewater treatment has been focused on its eco-friendly nature in terms of the improved energy conservation and reduction in carbon dioxide emissions. However, the anaerobic process discharges unrecovered methane as dissolved methane. In this study, to prevent the emission of dissolved methane from up-flow anaerobic sludge blanket (UASB) reactors used to treat sewage and to recover it as useful gas, we employed a two-stage down-flow hanging sponge (DHS) reactor as a post-treatment of the UASB reactor. The closed DHS reactor in the first stage was intended for the recovery of dissolved methane from the UASB reactor effluent; the reactor could successfully recover an average of 76.8% of the influent dissolved methane as useful gas (containing methane over 30%) with hydraulic retention time of 2 h. During the experimental period, it was possible to maintain the recovered methane concentrations greater than 30% by adjusting the air supply rate. The remaining dissolved methane after the first stage was treated by the next step. The second closed DHS reactor was operated for oxidation of the residual methane and polishing of the remaining organic carbons. The reactor had a high performance and the influent dissolved methane was mostly eliminated to approximately 0.01 mgCOD L(-1). The dissolved methane from the UASB reactor was completely eliminated--by more than 99%--by the post-treatment after the two-stage closed DHS system.

Effects of raloxifene and hormone replacement therapy on forearm skin elasticity in postmenopausal women.

OBJECTIVES: Hormone replacement therapy (HRT) increases skin elasticity in postmenopausal women. However, the effects of raloxifene, a selective estrogen receptor modulator (SERM), on skin degenerative changes in postmenopausal women remain unknown. We investigated whether raloxifene increases skin elasticity, similar to HRT, in postmenopausal women. METHODS: In a 12-month trial, 17 postmenopausal women (mean age, 66.4+/-7.8 years) received continuous raloxifene treatment (60 mg/day), 19 women (56.2+/-6.4 years) received continuous 17-beta estradiol treatment using a patch (0.72 mg/2 days) plus cyclic medroxyprogesterone acetate (2.5mg/day, for 12 days/month), and 11 women (58.1+/-7.3 years) did not receive either therapy. In each subject, the skin elasticity of the forearm was measured using a suction device at baseline and at 12 months after the start of the study. RESULTS: Raloxifene and HRT significantly increased skin elasticity from 52.4+/-3.8% and 64.1+/-7.2% at baseline to 55.1+/-4.7% and 67.4+/-7.4% after 12 months, respectively (P<0.05, each), but the untreated subjects did not exhibit any significant change in skin elasticity during the study. The delta value for skin elasticity was significantly higher among the raloxifene and HRT subjects than among the untreated subjects (P<0.05, each). CONCLUSIONS: These findings suggest that raloxifene may have a beneficial effect on skin elasticity, which undergoes degenerative changes in postmenopausal women, in addition to its effects on bone metabolism.

Impaired blood rheology and elevated remnant-like lipoprotein particle cholesterol in hypercholesterolaemic subjects.

Blood rheology, fasting serum concentrations of remnant-like lipoprotein particle cholesterol (RLP-C) and concentrations of other lipids were compared in 23 hypercholesterolaemic and 69 normocholesterolaemic subjects, and the relationship between red blood cell (RBC) deformability and RLP-C concentrations were studied in a different set of six hypercholesterolaemic and six normocholesterolaemic subjects. Passage time of whole blood and concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and RLP-C were significantly higher in hypercholesterolaemic than in normocholesterolaemic subjects. Passage time of whole blood correlated positively with TC, TG, LDL-C and RLP-C and negatively with high-density lipoprotein cholesterol. Furthermore, the passage time of 10% haematocrit-adjusted RBCs in phosphate-buffered saline, which reflects RBC deformability, correlated positively with the passage time of whole blood and RLP-C. Thus, hypercholesterolaemic subjects had impaired blood rheology and elevated RLP-C concentrations, which may be associated with the pathophysiology of atherosclerosis in hypercholesterolaemic subjects. Impaired RBC deformability may contribute to impaired blood rheology associated with elevated RLP-C in hypercholesterolaemic subjects.

A novel adipocytokine, visceral adipose tissue-derived serine protease inhibitor (vaspin), and obesity.

Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an interesting novel adipocytokine with insulin-sensitizing effects. Some studies have suggested that vaspin could play an important role in the development of obesity and metabolic disorders. The induction of vaspin mRNA expression could represent a compensatory mechanism associated with obesity, severe insulin resistance and type 2 diabetes mellitus, however it is unclear whether a correlation exists between human vaspin serum levels and markers of insulin sensitivity and glucose or lipid metabolism. Vaspin serum concentrations have been shown to be lower in lean subjects and competitive sportsmen with long-term physical training, but they are increased with weight loss associated with a physical training programme. In conclusion, there is at present no clear proof of a causal link between vaspin and visceral fat accumulation, or insulin resistance. This article reviews the role of vaspin in obesity-associated diseases and its potential as a new biomarker for obesity and impaired insulin sensitivity.

Chronic fatigue syndrome and the central nervous system.

An increasing amount of neuroimaging evidence supports the hypothesis that chronic fatigue syndrome patients have structural or functional abnormalities within the brain. Moreover, some neurotrophic factors, neurotransmitters and cytokines have also been evaluated in order to elucidate the mechanism of abnormal neuropsychic findings in chronic fatigue syndrome. In this review, we suggest that the focal point of chronic fatigue syndrome research should be transferred to the central nervous system.

Changes of microbial characteristics of retained sludge during low-temperature operation of an EGSB reactor for low-strength wastewater treatment.

In this study, a lab scale EGSB reactor was operated for 400 days to investigate the influence of temperature-decrease on the microbial characteristic of retained sludge. The EGSB reactor was started-up at 15 degrees C seeding with 20 degrees C-grown granular sludge. The influent COD of synthetic wastewater was set at 0.6-0.8 gCOD/L. The process-temperature was stepwise reduced from 15 degrees C to 5 degrees C during 400 days operation. Decrease of temperature of the reactor from 15 degrees C to 10 degrees C caused the decline of COD removal efficiency. However, continuous operation of the EGSB reactor led the efficient treatment of wastewater (70% of COD removal, 50% of methane recovery) at 10 degrees C. We confirmed that the both acetate-fed and hydrogen-fed methanogenic activities of retained sludge clearly increased under 15 to 20 degrees C. Changes of microbial profiles of methanogenic bacteria were analyzed by 16S rDNA-targeted DGGE analysis and cloning. It shows that genus Methanospirillum as hydrogen-utilizing methanogen proliferated due to low temperature operation of the reactor. On the other hand, genus Methanosaeta presented in abundance as acetoclastic-methanogen throughout the experiment.

Conjugated estrogen plus medroxyprogesterone does not impair blood rheological properties in hypertensive postmenopausal women.

OBJECTIVES: Hypertension and estrogens are both prothrombotic. We used the microchannel method to investigate whether hormone replacement therapy (HRT) with conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) affects blood flow through the microchannels in hypertensive postmenopausal women being treated with antihypertensive drugs and in normotensive postmenopausal women. METHODS: Sixty-two consecutive postmenopausal women were randomly assigned to a hypertensive HRT group (n=16), hypertensive control group (n=15), normotensive HRT group (n=16) and normotensive control group (n=15). Each HRT group received CEE 0.625 mg plus MPA 2.5 mg daily orally for 12 months. Both hypertensive groups were being treated with antihypertensive drugs before the study. Microvascular blood flow was assessed on the basis of blood passage time, the time required for 100 microl of whole blood to pass through a cylinder, was determined before and 12 months after the start of HRT by the microchannel method (micro channel array flow analyzer). RESULTS: CEE plus MPA therapy did not change blood passage time in any of the groups. Microscopic observation showed that the whole blood passed smoothly through the microchannels in every group. CONCLUSIONS: CEE plus MPA therapy may not impair blood flow through the microchannels in hypertensive postmenopausal women receiving antihypertensive drugs or in normotensive postmenopausal women. However, administration of CEE plus MPA to postmenopausal women with hypertension warrants caution against the occurrence of thromboembolic events.

Elevated arterial stiffness in postmenopausal women with osteoporosis.

OBJECTIVES: Osteoporosis and increased pulse wave velocity (PWV) are cardiovascular risk factors. We investigated the relationship between PWV and bone mass in the lumbar spine in postmenopausal women. METHODS: We studied the PWV in 95 women; 38 postmenopausal women with normal spinal bone mineral density (BMD), 32 osteopenic postmenopausal women, and 25 osteoporotic postmenopausal women. The brachial-ankle PWV (baPWV) was measured using an automated device. The BMD of the lumbar spine (L2-L4) was measured using dual-energy X-ray absorptiometry. RESULTS: After adjusting for age and years since menopause, women with osteoporosis had a significantly higher baPWV than those with normal BMD (1500 +/- 220 cm/s versus 1340 +/- 215 cm/s; P < 0.05), but no significant differences in baPWV were seen between the osteoporotic and osteopenic groups or between the osteopenic and normal BMD groups. In univariate regression analysis, the baPWV was significantly negatively correlated with BMD (r = -0.450, P < 0.01), and significantly positively correlated with age (r = 0.601, P < 0.01), years since menopause (r = 0.577, P < 0.01), systolic blood pressure (r = 0.295, P < 0.01), and diastolic blood pressure (r = 0.264, P < 0.05), but was not with other variables. In multivariate regression analysis, the baPWV was significantly correlated with BMD (P < 0.05), but not with other variables. CONCLUSIONS: Postmenopausal women with osteoporosis may have elevated arterial stiffness, suggesting that osteoporotic postmenopausal women may have a higher risk of cardiovascular disease.

Impaired blood rheology in critically ill patients in an intensive care unit.

Critically ill patients are at increased risk of thromboembolic complications. Japanese patients admitted to the intensive care unit of Gunma University Hospital were divided into critically ill (high score) and moderately ill (low score) groups according to mean Acute Physiology and Chronic Health Evaluation (APACHE) II score. White blood cell count, potassium, creatinine, immunoglobulin G and blood passage time, measured using the microchannel method, were significantly higher and the platelet aggregation score and platelet count were significantly lower in the high-score group than in the low-score group, but other haemorheological parameters did not differ significantly between the two groups. White blood cell count, potassium, creatinine, APACHE II score and levels of immunoglobulins G, A and M were positively correlated with blood passage time in all patients. Critically ill patients had impaired blood rheology, which could result from increased white blood cell count, potassium, creatinine and immunoglobulins and may be associated with the pathophysiology of the thromboembolic process.

Angiotensin-II receptor antagonist alleviates non-alcoholic fatty liver in KKAy obese mice with type 2 diabetes.

We examined the effects of the angiotensin-II receptor antagonist candesartan on non-alcoholic fatty liver (NAFL) and circulating adiponectin concentrations in KKAy obese mice with type 2 diabetes mellitus. The KKAy mice were randomly assigned to receive either candesartan at a once-daily dose of 10 mg/kg (n = 5) or placebo (n = 5). The differences in liver weight, histological evaluation of hepatic lipid infiltration, serum adiponectin concentration and hepatic adiponectin mRNA levels between the two groups were determined on day 7 after treatment was initiated. Candesartan-treated mice demonstrated significantly lower liver weights and reduced lipid droplets in hepatic cells compared with control mice. The circulating adiponectin levels and hepatic expression of adiponectin mRNA were significantly higher in candesartan-treated mice than control mice. These results suggest that candesartan might alleviate NAFL through elevation of circulating adiponectin levels in KKAy obese mice with type 2 diabetes mellitus.

Low strength wastewater treatment under low temperature conditions by a novel sulfur redox action process.

The objective of this research is to make a novel wastewater treatment process activated by a sulfur-redox cycle action of microbes in low temperature conditions. This action is carried out by sulfate-reducing bacteria (SRB) and sulfur-oxidizing bacteria (SOB). The process was comprised of a UASB reactor as pre-treatment and an aerobic downflow hanging sponge (DHS) reactor as post-treatment. As the results of reactor operation, the whole process achieved that over 90% of CODcr removal efficiency, less than 30 mgCODcr/L (less than 15 mgBOD/L) of final effluent, at 12 h of HRT and at 8 degrees C of UASB reactor temperature. Acetobacterium sp. was detected as the predominant species by PCR-DGGE method targeting 16SrDNA with band excision and sequence analysis. In the UASB reactor, various species of sulfate-reducing bacterium, Desulfobulbus sp., Desulfovibrio sp., and Desulfomicrobium sp., were found by cloning analysis. In the DHS reactor, Tetracoccus sp. presented as dominant. The proposed sulfur-redox action process was considered as an applicable process for low strength wastewater treatment in low temperature conditions.

Adiponectin replacement therapy attenuates myocardial damage in leptin-deficient mice with viral myocarditis.

The effects of adiponectin replacement therapy on myocardial damage were studied in leptin-deficient (OB) mice with acute viral myocarditis. Encephalomyocarditis virus was injected intraperitoneally into OB and wild-type (WT) mice. One subgroup of OB mice received no intervention and another subgroup received daily adiponectin replacement, simultaneously with viral inoculation. Differences in heart weight, cardiac histological score, numbers of infiltrating or apoptotic cells in the myocardium and the immunoreactivity of adiponectin receptors in myocytes were determined. The reactivity of adiponectin receptor 1 in myocytes from OB mice on day 4 and day 8 after viral inoculation was significantly decreased compared with that in myocytes from WT mice; the OB mice also had elevated cardiac weights and severe inflammatory myocardial damage. Adiponectin replacement in OB mice inhibited the development of severe myocarditis by augmenting myocyte adiponectin receptor 1 reactivity. Exogenously administered adiponectin may inhibit the progression of viral myocarditis through binding to the adiponectin receptor 1 in leptin-deficient conditions.

Adiponectin, T-cadherin and tumour necrosis factor-alpha in damaged cardiomyocytes from autopsy specimens.

This study determined the presence of adiponectin, T-cadherin (an adiponectin receptor) and tumour necrosis factor-alpha (TNF-alpha) in damaged myocytes from autopsied patients with acute or old myocardial infarction (MI) or dilated cardiomyopathy (DCM), using immunohistochemical staining. The enrolled patients included eight with acute MI, six with old MI and seven with DCM. Four autopsied individuals with no cardiac lesions were also enrolled as controls. Adiponectin and TNF-alpha were not observed in normal myocytes from control subjects, but T-cadherin was weakly detected. Immunoreactivity for adiponectin and T-cadherin was observed at the periphery of damaged myocytes from MI and DCM patients; intracellular reactivity for TNF-alpha was also seen. There were no statistically significant differences in the degree of reactivity for each molecule in the myocytes between the MI and DCM patients. These results suggest that the presence of adiponectin and TNF-alpha in damaged myocytes may contribute to the processes of myocardial injury occurring in MI and DCM.

Clinical features associated with circulating concentration of soluble leptin receptor in patients with diabetes.

We aimed to determine if there were any clinical features that were significantly associated with the circulating concentration of soluble leptin receptor (OB-Re) in 67 Japanese subjects with diabetes mellitus. The characteristics evaluated included age, height, body weight, body mass index (BMI), systolic and diastolic blood pressure, duration of diabetes, haemoglobin A1C and blood lipid concentrations, urinary albumin excretion rate, circulating concentrations of leptin, tumour necrosis factor-alpha (TNF-alpha), TNF-alpha receptor 1 and genotypes of the angiotensin-converting enzyme (ACE) gene. We found statistically significant negative correlations between circulating OB-Re concentration and body weight, BMI, diastolic blood pressure, concentrations of leptin and TNF-alpha receptor 1. Serum OB-Re concentration was not associated with any of the other clinical characteristics that were measured, or with the different ACE genotypes. Our results suggest that OB-Re might have an important influence on the biological activity of leptin in diabetic subjects.

Effect of antihypertensive therapy on blood rheology in patients with essential hypertension.

Hypertension is an important risk factor for cardiovascular disease, and antihypertensive drugs can decrease the occurrence of such events in hypertensive patients. This study compared the rheological properties of blood in 22 untreated hypertensive patients, 42 patients taking antihypertensive drugs and 74 normotensive subjects. Using a microchannel method, the whole blood passage time was measured and blood movement was observed with a microscope connected to an image display unit. The blood passage time in untreated hypertensive patients was significantly higher than in treated hypertensive patients or normotensive subjects, but was similar in the latter two groups. Microscopic observations showed that platelet aggregation and leucocyte adhesion were increased in untreated hypertensive patients, resulting in poor flow, while blood samples from treated hypertensive patients and normotensive subjects passed smoothly through the microchannels. These rheological differences could contribute to the decrease in cardiovascular disease seen when hypertensive patients are treated effectively.

Serum level of vascular endothelial growth factor is decreased by hormone replacement therapy in postmenopausal women without hypercholesterolemia.

The administration of hormone replacement therapy (HRT) to postmenopausal women (PMW) reportedly has beneficial effects on their levels of lipid and lipoproteins. Estrogen retards the development of atherosclerosis induced by a high-fat diet in animals. Although vascular endothelial growth factor (VEGF) may be involved in the development of atherosclerosis in humans, there is no information on effect of estrogen administration on VEGF level and lipid metabolism. We evaluated 64 healthy normotensive or hypertensive PMW before and during the administration of HRT (0.625 mg conjugated equine estrogen combined with 2.5 mg medroxyprogesterone acetate orally) daily for 6 months. All hypertensive PMW were well-controlled on antihypertensive drug therapy. According to their total cholesterol level at baseline, we divided the PMW with HRT (n=54) into a normocholesterolemic group (NC, total cholesterol <220 mg/dl, n=35) and a hypercholesterolemic group (HC, total cholesterol >/=220 mg/dl, n=19). We evaluated the serum levels of VEGF at baseline, and again at 3 and 6 months after starting HRT. HRT significantly (P<0.01) reduced the mean VEGF level from 31.5+/-4.3 pg/ml at baseline to 18.2+/-2.3 pg/ml after 6 months in the NC group. However, the VEGF levels in the HC group and the control group exhibited no significant change at either 3 or 6 months after starting HRT. In summary, HRT, using a combination of conjugated equine estrogen and medroxyprogesterone acetate, reduced the level of VEGF in normocholesterolemic PMW more effectively than in those with hypercholesterolemia.

Chronic blockade of nitric oxide synthesis increases urinary endothelin-1 excretion.

OBJECTIVES: Our objective was to determine the effect of nitric oxide (NO) inhibition on renal synthesis of endothelin-1 (ET-1) in vivo. DESIGN AND METHODS: Rats were administered 500 mg/l NG-nitro-L-arginine methyl ester (L-NAME) in their drinking water or its vehicle for 2 weeks (2W-L-NAME, n = 10; 2W-CONT, n = 10) or for 6 weeks (6W-L-NAME, n = 13; 6W-CONT, n = 11). We measured the levels of albumin, NO metabolites and ET-1 both in their blood and in 24 h urine samples, and determined the expression of preproET-1 messenger RNA in the renal cortex and the inner medulla. We also examined renal histology. RESULTS: L-NAME administration for 6 weeks reduced NO metabolites both in serum (21.5 versus 3.66 nmol/ml in 6W-CONT) and in urine (5.72 versus 22.53 nmol/24 h in 6W-CONT), raised the systolic blood pressure (228 versus 162 mmHg in 6W-CONT), and the increased urinary excretion of albumin (24.29 +/- 11.66 versus 0.60 +/- 0.08 mg/day in 6W-CONT) and of ET-1 (112.0 +/- 38.3 versus 35.8 +/- 4.4 pg/day in 6W-CONT). There were no significant differences between the plasma levels of ET-1 in the control and L-NAME groups. Expression of preproET-1 messenger RNA increased in the renal cortex but not in the inner medulla in the 6W-L-NAME group. Bleeding and marked arteriolar narrowing were observed in the renal cortex of the 6W-L-NAME group. CONCLUSIONS: Prolonged inhibition of NO synthesis increases urinary excretion of ET-1 and albumin without having any effect on plasma ET-1 levels. These results do not support the hypothesis that NO plays an inhibitory role in the regulation of ET-1 in the systemic circulation, although it is possible that such a role could exist in renal tissue. However, in view of the albuminuria, a more likely explanation is that increased urinary ET-1 is secondary to L-NAME-induced renal hyperfiltration injury.

Decreased basal production of nitric oxide in patients with heart disease.

STUDY OBJECTIVES: The pathophysiologic role of nitric oxide (NO) released in the lung is not well understood. To determine whether the production of endogenous NO is correlated with any hemodynamic parameters, we measured the amount of NO released from the lung tissue of patients with heart disease. METHODS: Twenty patients (14 with ischemic heart disease, 4 with dilated cardiomyopathy, and 2 with mitral stenosis) and 16 normal control subjects were enrolled in the study. We measured exhaled air samples by using a method developed in our laboratory. The NO release rate from the lungs was calculated from the amount of exhaled NO and the duration of the exhalation. RESULTS: The rate of NO release was significantly lower in the patients with moderate-to-severe heart failure (New York Heart Association [NYHA] II or III) than in those with mild heart failure (NYHA I) or in normal control subjects. The rate of NO release was positively correlated with the cardiac index (r=0.50, p<0.05), and was negatively correlated with either the systemic (r= -0.58, p<0.01) or pulmonary vascular resistance (r=-0.45, p<0.05). In the patients with moderate-to-severe heart failure, the amount of NO released and the oxygen tension in the pulmonary artery were significantly lower compared with those parameters in patients with mild heart failure. CONCLUSIONS: Results suggest that the basal production of endogenous NO in the lung tissue of patients with heart failure is impaired, perhaps leading to the elevated pulmonary vascular tone seen in patients with moderate-to-severe heart failure.

Effect of long-term hormone replacement therapy on angiotensin-converting enzyme activity and bradykinin in postmenopausal women with essential hypertension and normotensive postmenopausal women.

OBJECTIVE: Hormone replacement therapy (HRT) reduces the incidence of cardiovascular disease in postmenopausal women. Three-month short-term HRT in postmenopausal women with essential hypertension increased the plasma concentrations ofbradykinin with decreased serum angiotensin-converting enzyme (ACE) activity, which may be partially responsible for the cardioprotective effects of HRT. The objective was to determine whether 12-month long-term HRT in postmenopausal women with essential hypertension would maintain the decreased ACE activity and increased bradykinin levels and whether long-term HRT would increase the plasma bradykinin concentrations of normotensive postmenopausal women who had shown no significant changes in the 3-month HRT study, despite their decreased serum ACE activity. DESIGN: Twenty hypertensive and 15 normotensive postmenopausal women were treated with conjugated estrogens (0.625 mg/day) and medroxyprogesterone (2.5 mg/day) for 12 months. Twenty hypertensive and 15 normotensive postmenopausal women were used as controls. The controls were not treated with HRT. Serum ACE activity and plasma bradykinin concentrations were measured at baseline and at 12 months. RESULTS: Long-term HRT in both hypertensive and normotensive postmenopausal women significantly decreased serum ACE activity from 15.5+/-0.7 IU/L and 16.0+/-0.9 IU/L, respectively, at baseline to 13.3+/-0.5 IU/L and 14.2+/-0.9 IU/L, respectively, 12 months after the start of HRT (p < 0.05 and p < 0.05, respectively). Long-term HRT in both hypertensive and normotensive postmenopausal women also significantly increased plasma bradykinin concentrations from 22.1+/-4.4 pg/mL and 19.2+/-3.0 pg/mL, respectively, at baseline to 86.7+/-21.2 pg/mL and 73.5+/-23.0 pg/mL, respectively, 12 months after the start of HRT (p < 0.01 and p < 0.05, respectively). No significant changes in serum ACE activity or plasma bradykinin concentrations were observed in the control groups. CONCLUSIONS: Long-term HRT in hypertensive and normotensive postmenopausal women decreases their serum ACE activity and increases their plasma bradykinin concentrations. Thus, maintenance of elevated bradykinin with decreased serum ACE activity by HRT may be useful in reducing the risk of cardiovascular disease in both hypertensive and normotensive postmenopausal women.

Hormone replacement therapy increases plasma level of angiotensin II in postmenopausal hypertensive women.

The renin-angiotensin-aldosterone system plays a major role in the pathogenesis of hypertension by enhancing the production or the activity of angiotensin II (ANG II). We evaluated the effects of hormone replacement therapy (HRT) on the renin-angiotensin-aldosterone system and on bradykinin in postmenopausal women (PMW) who were hypertensive or normotensive. Subjects included 28 PMW whose elevated blood pressure (BP) was well controlled on antihypertensive agents excluding diuretics, angiotensin-converting enzyme (ACE) inhibitors, and ANG II receptor antagonists. As controls, we evaluated 16 normotensive PMW. All subjects received oral HRT daily for 6 months. The plasma levels of angiotensin I (ANG I), ANG II, and bradykinin as well as plasma renin activity (PRA) showed a significant increase in HRT in the hypertensive group, but not in the normotensive group. The serum ACE activity showed a significant decrease in both groups, but the plasma level of aldosterone was unchanged. Despite the decrease in serum ACE activity, there was an increase in the plasma ANG II level. Hormone replacement therapy increased the level of ANG II in the hypertensive women, but their BP was unaffected. The increase in plasma bradykinin level may maintain homeostasis in the presence of an increase in plasma ANG II, which is a risk factor for cardiovascular disease. Hormone replacement therapy was associated with a decrease in serum ACE and an increase in plasma bradykinin in hypertensive PMW. Accordingly, the protective effect of HRT against cardiovascular disease in PMW can be provided by a decrease in ACE activity and an increase in bradykinin.