Biomedical subjects

Kazuhito Totsune

Publications and source records attributed to Kazuhito Totsune.

At least 37 records · Page 2Linked to original sources

PubMed2005

White-coat hypertension as a risk factor for the development of home hypertension: the Ohasama study.

BACKGROUND: White-coat hypertension is a condition characterized by elevated blood pressure (BP) in medical settings combined with normal ambulatory-recorded BP or self-measured BP at home (home BP). However, it is unknown whether this condition represents a transient state in the development of hypertension outside medical settings. METHODS: We followed up 128 subjects with white-coat hypertension (home BP <135/85 mm Hg and office BP > or = 140/90 mm Hg) for 8 years and compared the risk of progression with home hypertension (home BP > or = 135/85 mm Hg or start of treatment with antihypertensive medication) with 649 sustained normotensive subjects (home BP <135/85 mm Hg and office BP <140/90 mm Hg) using data from population-based home BP measurement projects in Japan. RESULTS: During the 8-year follow-up period, 60 subjects (46.9%) with white-coat hypertension and 144 (22.2%) with sustained normotension progressed to home hypertension. The odds ratio of subjects with white-coat hypertension for progression to home hypertension (adjusted for possible confounding factors) was significantly higher than for subjects with sustained normotension (odds ratio, 2.86; P<.001). This association was observed independent of baseline home BP levels. CONCLUSION: The results from the present 8-year follow-up study demonstrate that white-coat hypertension is a transitional condition to hypertension outside medical settings, suggesting that white-coat hypertension may carry a poor cardiovascular prognosis.

Adult↗

PubMed2005

Use of 2003 European Society of Hypertension-European Society of Cardiology guidelines for predicting stroke using self-measured blood pressure at home: the Ohasama study.

AIMS: To evaluate the predictive power of the risk stratification system proposed in the 2003 European Society of Hypertension-European Society of Cardiology (2003 ESH-ESC) guidelines and to compare self-measured blood pressure at home (HBP) with casual-screening blood pressure (CBP) for prediction of first stroke among a general Japanese population. METHODS AND RESULTS: HBP and CBP were measured in 1702 subjects (> or = 40 years) who had no history of stroke and who were followed for an average of 11 years. The subjects were assigned to one of five groups with differential risk stratification according to the 2003 ESH-ESC criteria: average risk, low added risk, moderate added risk, high added risk, and very high added risk. Even in the low risk group a significantly high risk for stroke was observed, and there was a linear step up of stroke risk based on HBP, as well as on CBP. On the basis of HBP classification, a higher stroke incidence was observed in the high and very high groups compared with CBP classification. CONCLUSION: The risk stratification system proposed in the 2003 ESH-ESC guidelines is valid for the prediction of stroke in this Japanese study population, and has a stronger predictive power when based on HBP than on CBP. The results indicate the usefulness of HBP for the prediction of stroke risk in individuals.

Blood Pressure↗

PubMed2005

Effects of adipokines on expression of adrenomedullin and endothelin-1 in cultured vascular endothelial cells.

Obesity is a major risk factor for the development of hypertension. Adipokines may cause hypertension by acting both centrally and directly on the vascular vessels. We wished to clarify whether three adipokines, leptin, resistin and tumor necrosis factor-alpha, affect expression of adrenomedullin and endothelin-1 in vascular endothelial cells. Human umbilical vein endothelial cells were cultured for 24 h with leptin (1-10 nmol/l), resistin (1-10 nmol/l) or tumor necrosis factor-alpha (1-10 ng/ml). Expression of adrenomedullin and endothelin-1 was examined by radioimmunoassay and northern blot analysis. Immunoreactive-adrenomedullin in the medium and adrenomedullin mRNA expression levels were decreased by treatment of tumor necrosis factor-alpha time- and dose-dependently, whereas endothelin-1 secretion was not significantly changed by it. Leptin or resistin had no significant effects on expression of adrenomedullin or endothelin-1 in human umbilical vein endothelial cells. Under hypoxic conditions (1% O2), expression of both adrenomedullin and endothelin-1 was induced in these cells. Immunoreactive-adrenomedullin levels in the medium were decreased by treatment of tumor necrosis factor-alpha under hypoxia. Leptin or resistin had no significant effects on adrenomedullin or endothelin-1 expression also in hypoxia. These findings have raised the possibility that decreased expression of adrenomedullin by tumor necrosis factor-alpha may be related to the increased risk of hypertension and other cardiovascular diseases in obese subjects.

Adrenomedullin↗

PubMed2005

Determinants of the second derivative of the finger photoplethysmogram and brachial-ankle pulse-wave velocity: the Ohasama study.

BACKGROUND: We examined different characteristics of the second derivative of the finger photoplethysmogram (SDPTG) and brachial-ankle pulse wave velocity (BAPWV) for assessing arterial function in a large general population, along with the alteration of SDPTG in hypertension. METHODS: Finger SDPTG and BAPWV were measured in 848 (544 normotensive and 304 untreated hypertensive) subjects 34 to 88 years of age. For assessing SDPTG, we calculated the B:A and D:A ratios and the aging index (AGI), based on the height of the wave components. Using univariate and multivariate analyses, determinants of SDPTG indices and BAPWV as well as differences between normotensive and hypertensive subjects were evaluated. RESULTS: We found that BAPWV was independently and positively correlated with age, blood pressure (BP), heart rate (HR), and hemoglobin A1c. The D:A ratio and AGI showed a positive and the B:A ratio a negative independent correlation with age and BP. In contrast, the D:A ratio and AGI showed a negative and the B:A ratio a positive correlation with HR. The SDPTG indices, but not BAPWV, were independently associated with gender. The multivariate-adjusted D:A ratio, AGI, and BAPWV were significantly higher and the adjusted B:A ratio was lower in hypertensive than in normotensive subjects, and hypertensive subjects showed two-fold greater adjusted risks of having high D:A and low B:A ratios. The SDPTG indices and BAPWV were mildly correlated with each other in normotensive but not in untreated hypertensive subjects. CONCLUSION: Although the SDPTG depends on various factors in a manner different from BAPWV, it may be useful for detecting vascular aging accelerated by hypertension.

Adult↗

PubMed2005

Efficacy and duration of action of the four selective angiotensin II subtype 1 receptor blockers, losartan, candesartan, valsartan and telmisartan, in patients with essential hypertension determined by home blood pressure measurements.

Our objective was to compare the efficacy and duration of action of 4 angiotensin II receptor blockers (ARBs)--losartan (25-100 mg), candesartan (2-12 mg), valsartan (40-80 mg), and telmisartan (10-40 mg)-in patients with essential hypertension using self-measurement of blood pressure at home (home BP) and to examine the differential effect of the four ARBs on home pulse pressure (home PP). After a 2-week run-in period, each of the 4 ARBs was assigned to subjects who were diagnosed as having hypertension on the basis of home BP and who were over 30 years old. The subjects were asked to take the ARB once daily in the morning and to measure home BP once in the evening and in the morning. We compared the efficacy of each ARB on home BP and home PP and assessed the duration of the BP-lowering effect using the morning effect versus evening effect ratio (M/E ratio). The antihypertensive effects of telmisartan on home systolic BP (SBP) both in the evening and in the morning and on home diastolic BP (DBP) in the morning were significantly greater than those of losartan. The effect of each ARB on home BP in the morning and in the evening was expressed as a ratio (M/E ratio). The M/E ratios of SBP/DBP in patients treated with losartan, candesartan, valsartan, and telmisartan were 0.49/0.16, 0.69/1.01, 0.82/0.88, and 0.88/0.88, respectively. The home PP-lowering effect was greater for valsartan and telmisartan than for losartan and candesartan in the morning. Among the 4 ARBs, the duration of the BP-lowering effect of losartan did not persist throughout 24 hr. The effects of the other 3 ARBs, in particular telmisartan, persisted over 24 hr when they were administered once daily in the morning. In addition, the duration of the PP-lowering effect was similar to that of the BP-lowering effect. Such long-acting property of several ARBs is essential for the modern antihypertensive treatment, and home BP measurements are useful for determining the duration of action of antihypertensive drugs. Losartan, 25 mg a day, which is usually used as an initial dose in Japan, is apparently insufficient to obtain adequate antihypertensive effect and sufficient duration of action.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

Prevalence of masked uncontrolled and treated white-coat hypertension defined according to the average of morning and evening home blood pressure value: from the Japan Home versus Office Measurement Evaluation Study.

OBJECTIVE: To evaluate the prevalence of masked uncontrolled and treated white-coat hypertension defined according to the average of morning and evening home blood pressure values. METHODS: The study population consisted of 3303 essential hypertensive outpatients receiving antihypertensive treatment in Japan. Information on the characteristics of the patients was collected by a physician's self-administrated questionnaire. The office blood pressure value was calculated as the average of the four readings in two visits. All patients were asked to measure their blood pressure once every morning and once every evening. In the study, we included patients with at least three measurements in the morning and in the evening, respectively. The average of all home blood pressure values was taken as the home blood pressure value. RESULTS: The mean value of home systolic/diastolic blood pressure was 136.8/79.3 mmHg, and the mean value of office systolic/diastolic blood pressure was 142.8/80.6 mmHg. Of the 3303 patients, 758 (23.0%) had controlled hypertension (home <135/85 mmHg and office <140/90 mmHg), 628 (19.0%) had masked uncontrolled hypertension (home > or =135/85 mmHg and office <140/90 mmHg), 640 (19.4%) had treated white-coat hypertension (home <135/85 mmHg and office > or =140/90 mmHg), and 1277 (38.7%) had uncontrolled hypertension (home > or =135/85 mmHg and office > or =140/90 mmHg). CONCLUSIONS: Treated white-coat hypertension and masked uncontrolled hypertension were often observed in clinical settings. Physicians need to understand the prevalence of such patients to prevent inadequate diagnosis and treatment in them.

Adult↗

PubMed2005

Isolated uncontrolled hypertension at home and in the office among treated hypertensive patients from the J-HOME study.

OBJECTIVES: To evaluate the current status of blood pressure (BP) control as measured at home and in the office, as well as to clarify and compare the prevalence and characteristics of isolated uncontrolled hypertension as measured at home (home hypertension) and in the office (office hypertension). DESIGN: A cross-sectional study. SETTING: Primary care offices in Japan. PARTICIPANTS: A sample of 3400 patients with essential hypertension (mean age, 66 years; males, 45%) receiving antihypertensive treatment. RESULTS: Overall, the mean home systolic BP (SBP)/diastolic BP (DBP) was 140/82 mmHg, and the mean office SBP/DBP was 143/81 mmHg. Of the 3400 subjects, 19% had controlled hypertension (home SBP/DBP < 135/85 mmHg and office SBP/DBP < 140/90 mmHg), 23% had isolated uncontrolled home hypertension (home SBP/DBP >/= 135/85 mmHg and office SBP/DBP < 140/90 mmHg), 15% had isolated uncontrolled office hypertension (home SBP/DBP < 135/85 mmHg and office SBP/DBP < 140/90 mmHg), and 43% had uncontrolled hypertension (home SBP/DBP >/= 135/85 mmHg and office SBP/DBP >/= 140/90 mmHg). Compared to controlled hypertension, factors associated with isolated uncontrolled home hypertension included obesity, relatively higher office SBP, habitual drinking, and the use of two or more prescribed antihypertensive drugs. Compared to uncontrolled hypertension, factors associated with isolated uncontrolled office hypertension included female gender, lower body mass index, and relatively lower office SBP. CONCLUSIONS: The use of all four, three of four, or all three predictive factors might be useful for the clinician to suspect isolated uncontrolled home or office hypertension.

Aged↗

PubMed2005

Efficacy of combination antihypertensive therapy with low-dose indapamide: assessment by blood pressure self-monitoring at home.

We examined the effects of the addition of low-dose indapamide to antihypertensive drugs of other classes, as well as its duration of action, using blood pressure (BP) self-monitoring at home. Seventy-six patients undergoing monotherapy with a calcium channel blocker (CCB), angiotensin converting-enzyme inhibitor (ACEI), or angiotensin AT1-receptor blocker (ARB), but had an average morning home systolic BP (SBP) > or =135 mmHg or diastolic BP (DBP) > or =85 mmHg, were studied. Indapamide (1 mg) was added to their existing treatment once daily for 4 weeks. The additional hypotensive effects of indapamide were evaluated by casual and home BPs, and the results were compared among the three groups of subjects classified according to their initial drug treatment classes. The morning/evening (M/E) ratio of BP reduction was calculated to assess the duration of the effect. Overall, indapamide significantly (P < 0.001) lowered morning home BP (147 +/- 12/87 +/- 9 mmHg to 135 +/- 12/81 +/- 9 mmHg), evening home BP (138 +/- 15/79 +/- 10 mmHg to 126 +/- 12/73 +/- 9 mmHg), and casual BP (145 +/- 21/86 +/- 14 mmHg to 136 +/- 17/81 +/- 13 mmHg). All groups showed significant indapamide-induced home SBP/DBP decreases, whereas only the ACEI and ARB groups, but not the CCB group, showed a home pulse pressure (PP) reduction. Evening SBP and PP decreases were significantly greater in the ARB group than in the CCB group. The mean M/E ratio with indapamide was 0.95 for SBP and 0.85 for DBP. Low-dose indapamide used in combination can provide additional anti-hypertensive efficacy lasting for 24 h. The added effect of indapamide may be more prominent on ARBs than on CCBs.

Aged↗

PubMed2005

[Urotensin II].

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Animals↗

PubMed2004

Ambulatory blood pressure and 10-year risk of cardiovascular and noncardiovascular mortality: the Ohasama study.

The objective of this study was to elucidate the long-term prognostic significance of ambulatory blood pressure. Ambulatory and casual blood pressure values were obtained from 1332 subjects (872 women and 460 men) aged >or=40 years from the general population of a rural Japanese community. Survival was then followed for 14 370 patient years and analyzed by a Cox hazard model adjusted for possible confounding factors. There were 72 cardiovascular deaths during the 10.8-year follow-up. The relationship between 24-hour systolic blood pressure and the cardiovascular mortality risk was U-shaped in the first 5 years, then changed to J-shaped over the rest of the 10.8-year follow-up. After censoring the first 2 years of data, the risk flattened until it again increased for the fifth quintile of 24-hour systolic blood pressure for the 10.8-year follow-up period. For 24-hour diastolic blood pressure, the J-shaped relationship remained unchanged, regardless of follow-up duration and censoring. Ambulatory systolic blood pressure values consistently showed stronger predictive power for cardiovascular mortality risk than did casual systolic blood pressure in the 10.8-year follow-up data, whereas such relationships became more marked after censoring the first 2 years. When nighttime and daytime systolic blood pressure values were simultaneously included in the same Cox model, only nighttime blood pressure significantly predicted the cardiovascular mortality risk for the 10.8-year follow-up data. We conclude that the relationship between ambulatory systolic blood pressure and cardiovascular mortality is not U-shaped or J-shaped, and that nighttime blood pressure has better prognostic value than daytime blood pressure.

Aged↗

PubMed2004

Prediction of stroke by self-measurement of blood pressure at home versus casual screening blood pressure measurement in relation to the Joint National Committee 7 classification: the Ohasama study.

BACKGROUND AND PURPOSE: To compare the predictive power of self-measured home blood pressure (HBP) and casual blood pressure (CBP) for stroke risk in relation to the Joint National Committee 7 (JNC-7) classification. METHODS: HBP and CBP measurements were taken in 1702 subjects (> or =40 years) without a history of stroke, who were followed up for an average of 11 years. Subjects were classified into 4 groups on the basis of either HBP or CBP, according to the JNC-7 criteria: group 1 (HBP <115/75 mm Hg; CBP <120/80 mm Hg); group 2 (115/75< or =HBP<135/85 mm Hg; 120/80< or =CBP<140/90 mm Hg); group 3 (135/85< or =HBP<150/95 mm Hg; 140/90< or =CBP<160/100 mm Hg); and group 4 (HBP> or =150/95 mm Hg; CBP > or =160/100 mm Hg). Groups 2, 3, and 4 were further divided into 2 subgroups (a and b): those without and with cardiovascular disease risks, respectively. The risk of the first stroke in these groups was examined by the Cox hazards model adjusted for age and sex. RESULTS: The stroke risk in groups 3b and 4b (defined by HBP and CBP) was 2 to 5x higher than that in group 1 with significant differences. The risk in groups 2a, 3a, and even 4a was not significantly different from that in group 1 by the CBP-based classification, but the risk in group 4a was significantly higher than that in group 1 by the HBP-based classification, which also showed a stepwise increase in risk from groups 2a to 4a. CONCLUSIONS: The JNC-7 classification had a stronger predictive power using HBP-based classification compared with CBP-based classification, suggesting the usefulness of HBP in the management of hypertension.

Aged↗

PubMed2004

Urocortins as cardiovascular peptides.

Urocortins (Ucn) 1, 2 and 3, human homologues of fish urotensin I, form the corticotropin-releasing factor (CRF) family, together with CRF, urotensin I and sauvagine. Ucn 3 is a novel member of this family and is a specific ligand for CRF type 2 receptor. CRF type 2 receptor is thought to mediate the stress-coping responses, such as anxiolysis, anorexia, vasodilatation, a positive inotropic action on myocardium and dearousal. Endogenous ligands for the CRF type 2 receptor expressed in the cardiovascular tissues, such as the myocardium, have long been unknown. We have shown expression of Ucn 3 as well as Ucn 1 in the human heart. Ucn 3 is also expressed in the kidney, particularly distal tubules. Studies in various rat tissues showed that high concentrations of immunoreactive Ucn 3 were found in the pituitary gland, adrenal gland, gastrointestinal tract, ovary and spleen in addition to the brain, heart and kidney. These observations suggest that Ucn 3 is expressed in various tissues including heart and kidney, and may regulate the circulation in certain aspects of stress and diseases, such as inflammation. Ucn 1 and 3 appear to have important pathophysiological roles in some cardiovascular diseases.

Animals↗

PubMed2004

Elevated plasma levels of immunoreactive urotensin II and its increased urinary excretion in patients with Type 2 diabetes mellitus: association with progress of diabetic nephropathy.

Urotensin II (UII) is the most potent vasoconstrictor peptide ever identified. In order to clarify the pathophysiological role of UII in diabetes mellitus, we examined plasma immunoreactive UII levels and urinary excretion of immunoreactive UII in 10 control subjects and 48 patients with Type 2 diabetes mellitus. The patients were divided into three groups according to the renal function: Group I with Ccr > or = 70 ml/min, group II with 30 < or = Ccr <70 ml/min and group III with Ccr <30 ml/min. Plasma immunoreactive UII levels were elevated in the three diabetic groups compared with normal controls (P <0.05). Group III patients had significantly higher plasma immunoreactive UII levels (15.9 +/- 2.2 fmol/ml, mean +/- S.E.M., n=6) by approximately 1.6-fold than did group I (10.9 +/- 0.9 fmol/ml, n=17) and group II (10.8 +/- 0.8 fmol/ml, n=25) (P <0.05). Urinary excretion of immunoreactive UII was significantly increased in group III patients (52.4 +/- 14.8 pmol/day) by more than 1.8-fold compared with control subjects, groups I and II (P <0.005). Fractional excretion of immunoreactive UII significantly increased as renal function decreased. Presence of diabetic retinopathy or neuropathy had negligible effects on plasma immunoreactive UII levels and urinary immunoreactive UII excretion. Reverse phase HPLC analyses showed three immunoreactive peaks in normal plasma extracts and multiple immunoreactive peaks in normal urine extracts. Thus, Type 2 diabetes mellitus itself is a factor to elevate plasma immunoreactive UII levels, and accompanying renal failure is another independent factor for the increased plasma immunoreactive UII levels in Type 2 diabetic patients. Increased urinary immunoreactive UII excretion in Type 2 diabetic patients with advanced diabetic nephropathy may be due not only to the elevated plasma immunoreactive UII levels but also to increased UII production and/or decreased UII degradation in the diseased kidney.

Adult↗

PubMed2004

How many times should blood pressure be measured at home for better prediction of stroke risk? Ten-year follow-up results from the Ohasama study.

OBJECTIVE: To determine the optimum number of blood pressure self-measurements taken at home (home blood pressure) in relation to their predictive value for stroke risk. METHODS: We obtained more than 14 measurements of home blood pressure from 1491 people aged >or=40 years without a history of stroke in the general population in Japan, and followed them up after a mean period of 10.6 years. The prognostic significance of blood pressure for stroke risk was examined using the Cox proportional hazards regression model, which was adjusted for possible confounding factors. RESULTS: The predictive value of home blood pressure increased progressively with the number of measurements, showing the highest predictive value with the average of whole measurements (mean = 25 measurements, 35% increase in the risk of stroke per 10 mmHg elevation in blood pressure). The initial home blood pressure values (one measurement) showed a significantly greater relation with stroke risk than conventional blood pressure values (mean of two measurements) (19/8% increase in the risk of stroke per 10 mmHg elevation in initial home/conventional systolic blood pressure values, respectively). CONCLUSIONS: There was no threshold for the number of home blood pressure measurements within the range of 1-14 measurements for increasing the predictive power of stroke risk, suggesting that as many measurements as possible, preferably more than 14 measurements, is recommended for better prediction of stroke risk. It should be emphasized that home blood pressure has a stronger predictive power than does conventional blood pressure, even for a lower number of measurements.

Adult↗

PubMed2004

The second progress report on the Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study.

BACKGROUND: The Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study is a large-scale intervention trial to determine both optimal target blood pressure (BP) on the basis of self-measured BP at home, and optimal initial antihypertensive medication. OBJECTIVE: To investigate the quality of randomization at the end of March 2003, and BP-controlled conditions during initial 6 months. METHODS: We evaluated the number of patients randomized by the end of March 2003, and BP changes during the initial 6 months based on intention-to-treat analysis. RESULTS: By the end of March 2003, a total of 1086 patients (12% of a planned randomization of 9000 patients) had been randomized. Among 653 patients who had been followed for > or =6 months after randomization, mean systolic/diastolic BPs at randomization in the calcium antagonist, angiotensin-converting enzyme and angiotensin II receptor blocker groups were 149/89, 150/89 and 149/88 mmHg, respectively. Blood pressures were reduced after 3 months (137/83, 139/82 and 136/82 mmHg, respectively), and further reduced after 6 months (134/81, 135/80 and 133/80 mmHg, respectively), with no significant differences identified between groups. In more- and less-intensive BP-lowering groups, mean systolic/diastolic BPs at randomization were 149/88 and 150/89 mmHg, respectively. Although BPs were reduced after treatment for 3 months (137/83 and 137/82 mmHg, respectively) and 6 months (134/80 and 135/80 mmHg, respectively) in each target group, significant differences were still not observed between groups. CONCLUSIONS: Good quality of randomization was observed at the end of March 2003, but rate of achievement for target BPs was insufficient.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2004

Prediction of ischaemic and haemorrhagic stroke by self-measured blood pressure at home: the Ohasama study.

OBJECTIVE: To examine the predictive value of self-measured blood pressure values taken at home (home blood pressure) for risk of stroke and subtypes. METHODS: We obtained home blood pressure measurements from 1702 people, aged > or =40 years, without a history of stroke, in the general population in Japan, and continued follow-up after a mean period of 10.6 years. The prognostic significance of blood pressure for stroke risk was examined using the Cox proportional hazards regression model, which was adjusted for possible confounding factors. RESULTS: There was a linear relationship between home blood pressure and risk of stroke and subtypes. On average, each 10/5 mmHg elevation in home systolic/diastolic blood pressure respectively, was associated with an approximately 30/20% respectively, higher risk of total stroke. A similar relationship was observed for the risk of haemorrhagic stroke (intracerebral and subarachnoid haemorrhage), and the risk of ischaemic stroke [cerebral infarction and transient ischaemic attack (TIA)]. The risk of stroke and subtypes showed a significantly greater relation with home blood pressure values compared to conventional blood pressure values. CONCLUSIONS: This is the first study to demonstrate that home blood pressure is an independent predictor for haemorrhagic and ischaemic stroke, in the general population.

Adult↗

PubMed2004

Suppression of cytokine-induced expression of endothelin-1 by dexamethasone in human retinal pigment epithelial cells.

We have recently shown that retinal pigment epithelial cells secrete endothelin-1 (ET-1). In the present study, we studied effects of cytokines and dexamethasone on expression of ET-1 in two types of cultured human retinal pigment epithelial cells, ARPE- 19 cells and D407 cells. Treatment for 24 hours with a combination of three cytokines, interferon-gamma, tumor necrosis factor-alpha and interleukin-1beta, induced expression of ET-1 in both cells. When treated with dexamethasone (10(-7) mol/L) alone, the immunoreactive endothelin level in the medium increased about three-fold in D407 cells, but not in ARPE-19 cells. Dexamethasone (10(-7) mol/L), however, suppressed the cytokine-mediated increases in ET-1 mRNA expression levels and immunoreactive endothelin levels in the medium. These findings raise the possibility that antiinflammatory effects of dexamethasone in eyes may be partly mediated or modulated by its effects on expression of ET-1.

Anti-Inflammatory Agents↗

PubMed2004

Expression of urocortin III/stresscopin in human heart and kidney.

Urocortin III (Ucn III)/stresscopin (SCP) is a novel peptide of the corticotropin-releasing factor (CRF) family and is a specific ligand for the CRF type 2 receptor. We wished to clarify whether Ucn III/SCP is expressed in the human heart and kidney. Immunoreactive Ucn III was detected by RIA in the human heart (0.74-1.15 pmol/g wet weight, mean +/- SEM; n = 4) and kidney (1.21 +/- 0.30 pmol/g wet weight), which were obtained at autopsy. These levels were comparable to the levels in pituitary (2.72 +/- 0.13 pmol/g wet weight; n = 3) and brain tissues ( approximately 1-2 pmol/g wet weight). Furthermore, immunoreactive Ucn III was present in human plasma (51.8 +/- 16.0 pmol/liter; n = 5) and urine (266 +/- 20 pmol/liter; n = 5) obtained from healthy subjects. Reverse-phase HPLC showed a broad peak of immunoreactive Ucn III eluting in the position of synthetic Ucn III in the heart, kidney, and hypothalamus. Material eluting in the position of SCP was also found in the HPLC analysis of these tissue extracts. Immunocytochemistry showed positive staining of Ucn III in the myocardium and the renal tubules, particularly distal tubules. RT-PCR showed expression of Ucn III mRNA in the brain, pituitary, heart, and kidney. The present study has shown expression of Ucn III/SCP in the human heart and kidney as well as brain and pituitary tissues and its presence in plasma and urine. Ucn III/SCP may therefore regulate the cardiac and renal function as a local factor and a circulating hormone.

Adult↗