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Biomedical subjects

O F Wagner

Publications and source records attributed to O F Wagner.

At least 19 recordsLinked to original sources
PubMed2006

Fibrinolytic dysfunction in insulin-resistant women with previous gestational diabetes.

BACKGROUND: Women with a history of gestational diabetes (p-GDM) are at increased risk of developing type 2 diabetes mellitus (DM2) later in life, and therefore at increased risk for future cardiovascular disease. MATERIALS AND METHODS: Three months after delivery we investigated the plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (t-PA), fibrinogen and von Willebrand factor (vWF) in 74 women with p-GDM and 20 healthy females with normal glucose tolerance during and after pregnancy, as well as the relation of fibrinolytic parameters to insulin resistance and glycaemic control. All women underwent an oral (OGTT) as well as an intravenous glucose tolerance test (FSIGT). Mathematical model analysis disclosed that 50% (n=37 each) of the p-GDM subjects had normal (NIS) or impaired (IIS) insulin sensitivity. Parameters of interest were determined using commercially available test systems. RESULTS: Women with p-GDM and IIS had significantly increased body fat mass (BFM) (P<or=0.001) compared with women with p-GDM and NIS and controls, whereas the waist to hip ratio (WHR) was similar in both p-GDM groups but was higher compared with the controls (P<or=0.001). Mean PAI-1 and t-PA as well as fasting and stimulated plasma concentrations of proinsulin, C-peptide and insulin were elevated, whereas the disposition index was lower in women with p-GDM and IIS compared with women with p-GDM and NIS and the controls (P<0.001). Plasma levels of fibrinogen and vWF did not differ between the groups. Obese women with IIS had higher PAI-1 levels than lean women with IIS (P<or=0.001). PAI-1 inversely correlated with the insulin sensitivity index (SI) but only in women with IIS (P<0.0001). On regression analysis, only fasting proinsulin and WHR remained significant independent predictors of PAI-1 elevation in IIS (P<or=0.0001 and P<or=0.001). The PAI-1/SI ratio was elevated in women with IIS independently of their glucose tolerance status (P<0.001 vs. NIS and controls). CONCLUSIONS: Plasminogen activator inhibitor type 1 is elevated in p-GDM women with IIS and depends on plasma proinsulin and abdominal obesity. An increase of the PAI-1/SI ratio further characterizes obese insulin-resistant p-GDM women who may be at risk for diabetes and angiopathy.

Adult↗
PubMed2006

Insulin sensitivity during oral glucose tolerance test and its relations to parameters of glucose metabolism and endothelial function in type 2 diabetic subjects under metformin and thiazolidinedione.

AIM: This study was designed to assess the usefulness of a model-based index of insulin sensitivity during an oral glucose tolerance test (OGTT) in the identification of possible changes in this metabolic parameter produced by pharmacological agents known to be potent insulin sensitizers, that is metformin (M) and thiazolidinedione (T). The association of these agents with several other factors related to glucose metabolism was also investigated, as well as the relation of insulin sensitivity and secretion with markers of endothelial function such as different adhesion molecules (cAMs), that is vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and E-Selectin. METHODS: Twenty type 2 diabetic patients treated with diet only underwent a 3-h OGTT for measurement of plasma glucose, insulin, proinsulin, C-peptide and cAMs before and after administration of randomly given M (n = 9; 1700 mg/day) or T (n = 11; 600 mg/day). After 16 weeks of treatment, a second OGTT was performed. Insulin sensitivity was calculated with homeostasis model assessment and with oral glucose insulin sensitivity (OGIS), which quantifies dynamic glucose clearance per unit change of insulin. Insulin secretion was assessed by modelling technique. Differences in these parameters before and after treatment, as well as possible relationships with cAMs, were assessed. RESULTS: Basal and stimulated plasma glucose decreased after therapy in both the groups by approximately 20%. Basal insulin resistance also decreased. Insulin sensitivity in dynamic conditions (OGIS: ml/min/m(2)) increased with M (289.3 +/- 18.8 vs. 234.7 +/- 18.1, p < 0.02) and tended to improve with T (323.5 +/- 18.1 vs. 286.8 +/- 22.1, p = 0.09). Total insulin secretion over the OGTT [TIS: nmol/l(3 h)] tended to decrease with M (17.1 +/- 2.5 vs. 27.3 +/- 0.3, p = 0.08) but not with T (23.6 +/- 3.5 vs. 22.5 +/- 2.7). Plasma concentrations of E-Selectin decreased in T (38.0 +/- 2.3 vs. 51.2 +/- 6.1 ng/ml, p < 0.05). No correlation was found between insulin sensitivity and cAMs. CONCLUSIONS: Model-based indices of insulin sensitivity and secretion during an OGTT can be able to detect changes observed in patients under treatment with pharmacological agents such as M or T. Both the drugs improved glucose control similarly. Decreased plasma E-Selectin concentrations were seen in patients on T therapy only.

Blood Glucose↗
PubMed2002

Circulating concentrations of asymmetrical dimethyl-L-arginine are increased in women with previous gestational diabetes.

AIMS/HYPOTHESIS: The concentration of asymmetrical dimethyl- L-arginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, is increased in patients at risk or with cardiovascular disease. We have investigated ADMA concentrations in women with a history of gestational diabetes (GDM), who could develop endothelial dysfunction and Type II (non-insulin-dependent) diabetes mellitus after delivery, and in healthy control subjects. METHODS: Previous GDM patients were grouped according to their BMI as obese (> or =25 kg/m(2), n=46) or non-adipose (<25 kg/m(2), n=31). Serum samples were taken 14 to 16 weeks after delivery and after 1 year. The control group comprised 17 healthy women (BMI<25 kg/m(2)). ADMA concentrations were analysed by high performance liquid chromatography. RESULTS: ADMA concentrations were comparable between obese and non-adipose GDM patients (0.58+/-0.02 and 0.57+/-0.02 micro mol/l, respectively), and higher than in the control group (0.47+/-0.03 micro mol/l; p<0.006). Insulin resistance as estimated by the insulin sensitivity index was more frequent among the obese than the non-adipose GDM women (p<0.05) and control subjects (p<0.05, both). No change in ADMA concentrations was found after 1 year in women with GDM. There was only a slight correlation between ADMA and BMI (r=0.26, p<0.02), triglycerides (r=0.29, p<0.004), or fasting plasma glucose (r=0.21, p<0.05), and not with the insulin sensitivity index or other parameters. In a multiple regression analysis ADMA serum concentrations were only associated with triglycerides. CONCLUSION/INTERPRETATION: Circulating ADMA concentrations are increased in normoglycaemic women with previous GDM. This increase is independent from other risk factors or surrogate markers for diabetes or cardiovascular events.

Adult↗
PubMed2002

Effects of enalapril and losartan on circulating adhesion molecules and monocyte chemotactic protein-1.

At least four independent studies in different clinical settings showed that angiotensin-converting enzyme inhibitors (ACE-Is) such as enalapril effectively decrease plasma levels of circulating adhesion molecules (cAMs). To examine whether this effect may be mediated by the decreased action of angiotensin, we compared the effects of enalapril with the direct angiotensin-II antagonist, losartan, on plasma levels of cAMs, and monocyte chemotactic protein-1 (MCP-1). In a randomized trial, we recruited 32 untreated patients (19 male, aged 59+/-13 years) with hypertension, who received either enalapril (mean dose 17 mg/day) or losartan (mean dose 77 mg/day) at equipotent doses. Enalapril decreased plasma levels of all cAMs after 8 weeks of treatment: cE-selectin levels decreased by 13% (P=0.007), intercellular adhesion molecule-1 (cICAM-1) by 15% (P=0.002) and vascular cell adhesion molecule-1 (cVCAM-1) by 19% (P=0.003). Similarly, enalapril decreased plasma levels of MCP-1 by 13% (P<0.001). Losartan did not significantly change cAM or MCP-1 plasma concentrations after 8 weeks of treatment: cE-selectin levels decreased by 3%, cICAM-1 by 5%, cVCAM-1 by 8%, whereas MCP-1 increased by 2% (all P=NS; not significant). The enalapril effect on percentage changes of cVCAM-1 was significantly different from losartan (P=0.0429). Eight weeks of antihypertensive treatment with enalapril but not losartan, significantly decreased plasma levels of cAMs and MCP-1 in hypertensive patients. The beneficial effects of ACE-Is on cAMs may have implications for atherogenesis and the reduction of cardiovascular events, which cannot be fully explained by their antihypertensive effects alone.

Aged↗
PubMed2001

Sex differences in HAART-associated dyslipidaemia.

OBJECTIVES: Because female sex protects against dyslipidaemia and atherosclerosis in normal subjects, we aimed to reveal potential sex differences in metabolic side-effects of a newly initiated highly active antiretroviral therapy (HAART) regimen, and to relate these changes to endothelial cell activation as measured by levels of circulating E-selectin (cE-selectin). DESIGN: Prospective longitudinal cohort study. SETTING: Tertiary care centre at a University Hospital. METHODS: HIV-seropositive male (n = 27) and female patients (n = 13) with a plasma viral load of > or = 10 000 copies/ml and 35 healthy controls were enrolled in the study. All participants were weight stable, free of acute opportunistic infections, and had not taken any protease inhibitors before. Serum levels of lipids, insulin, leptin, and cE-selectin were measured before initiation of HAART, and at 3 and 6 months thereafter. RESULTS: HAART increased serum levels of triglycerides, leptin, and low-density lipoprotein (LDL) cholesterol; these effects were more distinct in women. Fasting insulin levels and the LDL : high density lipoprotein (HDL) ratio increased only in female HIV-infected patients (P < 0.02 versus men). In contrast, endothelial activation, as measured by cE-selectin, decreased more in men (P < 0.02) than in women. As a consequence, women had higher triglycerides and leptin levels after therapy than did men, and the LDL : HDL ratio and cE-selectin levels, which were initially higher in men, were no longer different between the sexes. CONCLUSIONS: Metabolic adverse effects during HAART are more pronounced in women than in men. Hence, female HIV-infected patients seem to loose part of their natural protection from atherosclerosis during antiretroviral therapy.

Adult↗
PubMed2001

Recent insights into the molecular genetics of the homocysteine metabolism.

The homocysteine plasma level is determined by non-genetic and genetic factors. In recent years evidence has accumulated that the total homocysteine plasma level of patients under different forms of renal replacement therapy is influenced by a common mutation at nucleotide position 677 of the gene coding for 5,10-methylenetetrahydrofolate reductase (MTHFR 677C-->T). Furthermore, compound heterozygosity for the 677T allele and a novel A-->C polymorphism at nucleotide position 1298 of MTHFR is suggested to correlate with a decrease of folate plasma concentrations. Because polymorphisms of genes coding for proteins involved in the metabolism of homocysteine may contribute to elevated total homocysteine plasma concentrations, molecular genetic analyses of the homocysteine pathways experienced a drift towards screening for candidate genes with a putative relationship to total homocysteine plasma levels. One example is the cloning of the FOLR1 gene coding for the folate-binding protein (Folbp1), which has recently been inactivated in mice, thus representing an elegant model to investigate the consequence on the homocysteine metabolism. Furthermore, the recent characterization of the CUBN gene encoding the intrinsic factor-vitamin B12 receptor (cubilin) provides a basis to identify the causative mutations in patients suffering from a hereditary syndrome of hyperhomocysteinemia that presents with megaloblastic anemia and proteinuria. This review focuses on recent insights into the molecular genetics of MTHFR, FOLR1, and CUBN, and their relationships to the metabolism of the amino acid homocysteine.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed2000

Dexamethasone lowers circulating E-selectin and ICAM-1 in healthy men.

Plasma levels of circulating adhesion molecules (AMs) are increased in a number of inflammatory and cardiovascular disorders. Yet the mechanisms regulating the physiologic levels of soluble AMs are largely unknown. It has recently been postulated that glucocorticoids may exert their anti-inflammatory actions partially through the inhibition of cytokine-stimulated expression of E-selectin and intercellular adhesion molecule (ICAM-1). However, it remains controversial whether glucocorticoids affect the basal expression of AMs on resting cells. We have thus evaluated the effects of glucocorticoids by infusing therapeutic doses of dexamethasone (0.04 mg/kg and 1.0 mg/kg twice a day for 2 days) or placebo on plasma levels of circulating E-selectin (cE-selectin), soluble thrombomodulin (sTM), circulating ICAM-1 (cICAM-1), and circulating vascular cell adhesion molecule (cVCAM-1) in 9 healthy men. Plasma was obtained before infusion at 24 and 48 hours. Compared with baseline, levels of cE-selectin decreased by 16% and 22% with the lower and the higher doses, respectively, at 48 hours (P = .007), whereas sTM was unchanged. Both doses of dexamethasone reduced cICAM-1 by about 15% at 48 hours (P = .007), but there were no changes in cVCAM. Dexamethasone time-dependently decreases plasma levels of cE-selectin and cICAM-1 in healthy men. This demonstrates that a glucocorticoid-sensitive mechanism specifically down-regulates normal plasma levels of cE-selectin and cICAM-1 in healthy subjects, which could thus reflect minor baseline inflammation.

Adult↗
PubMed2000

Effects of hyperinsulinemia on plasma levels of circulating adhesion molecules.

Plasma levels of circulating intercellular adhesion molecule-1 (cICAM-1), a potential cardiovascular risk factor, are increased in diabetics. Among other factors, hyperinsulinemia has been proposed to enhance its release into the circulation. Thus, we directly examined the effects of insulin infusion on plasma levels of circulating adhesion molecules, and two other endothelial markers, i.e. von Willebrand factor (vWF) and soluble thrombomodulin (sTM). The study design was balanced, randomized, placebo-controlled, double blind, and cross-over. Twelve healthy male subjects received, on separate study days, a euglycemic hyperinsulinemic clamp (3 mU/kg x min) or placebo over 6 h. Plasma levels of cICAM-1, vascular cell adhesion molecule-1, circulating E-selectin, and sTM were measured by enzyme immunoassay; vWF-Ag was measured using a STA clot analyzer. Plasma levels of these adhesion molecules and endothelial cell activation markers were not affected despite a 30-fold increase in insulin levels. Hyperinsulinemia has no adverse effect on circulating ICAM-1, vascular cell adhesion molecule-1, E-selectin, vWF, or sTM and therefore does not directly induce endothelial activation.

Adult↗
PubMed1999

[Trends in molecular diagnosis].

The number of characterized monogenic and polygenic diseases is rising each year. In consequence, molecular diagnostics is faced with an ever increasing number of patient samples and with more and more heterogeneous genetic defects. The fusion of microelectronics and molecular biology has created a new technology (microelectronic miniaturization), which provides a rapid, efficient, and cost-effective tool in molecular diagnostics at a high-sample throughput. The biochip has recently been selected as one of the ten scientific highlights in the year 1998. The application of microelectronics ranges from the polymerase chain reaction (PCR), nucleotide sequence analysis via DNA-chips or capillary electrophoresis-chips to gene expression analysis. These microchips are suited for integration into fully automated systems, thus providing the basis for automation of molecular diagnostics. The present article summarizes important trends in molecular diagnostics and provides a glimpse on future technologies.

Diagnostic Techniques and Procedures↗
PubMed1999

Fosinopril decreases levels of soluble vascular cell adhesion molecule-1 in borderline hypertensive type II diabetic patients with microalbuminuria.

Angiotensin converting enzyme inhibitors (ACE-I) are a mainstay for the treatment of heart failure, and of diabetic microalbuminuria. Recently ACE-I have been found to decrease plasma levels of circulating vascular cell adhesion molecule-1 (cVCAM-1) in patients with congestive heart failure. As increased cVCAM-1 levels are pathognomonic for diabetics with microangiopathy, we investigated the effects of ACE-I on plasma levels of cVCAM-1, intercellular adhesion molecule (cICAM-1), and cE-selectin in microalbuminuric diabetics. In addition, the effects of ACE-I on plasma levels of plasminogen activator inhibitor (PAI-1) and of tissue plasminogen activator (TPA) were studied. Fosinopril (10 mg/day) was administered over 12 weeks to 11 microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM). As expected, baseline plasma concentrations of cE-selectin, cICAM-1, and cVCAM-1 were markedly higher in patients than in healthy control subjects (n = 82; P < .001). PAI-1 levels in NIDDM were similar to those in control subjects, whereas TPA levels were about 25% lower in patients than in control subjects (P = .013). Serum levels of cVCAM-1 decreased by -19% (CI: -25% to -13%) after treatment with fosinopril (P = .003) and were no longer different from those of the control group. In contrast, plasma levels of cE-selectin, cICAM-1, PAI-1, and TPA were unaffected. As expected microalbuminuria decreased by -44% (CI: -65 to -22; P = .004). In conclusion, fosinopril lowered cVCAM-1 levels along with microalbuminuria in NIDDM. This may represent a novel mechanism of action of ACE-I in diabetes-associated endothelial dysfunction. Whether decreased VCAM-1 expression is responsible for the observed reduction in microalbuminuria, deserves further investigation.

Adult↗
PubMed1999

Activation of endothelium by immunotherapy with interleukin-2 in patients with malignant disorders.

Treatment with intravenous recombinant human interleukin-2 (rh IL-2) is frequently accompanied by the capillary leak syndrome and disturbances of the coagulation system. Although the exact mechanisms are still not fully understood, the involvement of the endothelium is proven. This investigation aimed to elucidate more precisely the role of the endothelium in the generation of IL-2-based side-effects. In nine tumour patients receiving intravenous rh IL-2, parameters characterizing endothelial cell activation as well as activation of the coagulation system were evaluated. A significant increase of the circulating endothelial leucocyte adhesion molecule-1 (cELAM-1) and the vasoconstrictor peptide endothelin-1 (ET-1) was observed (P<0.05), indicating activation of endothelial cells. The simultaneous increase of tissue-plasminogen activator and plasminogen activator inhibitor type-1 during therapy (P<0.05) corroborated this observation. A decrease in platelet count parallelled by an increase of fibrin degradation products, the prolongation of partial thromboplastin time, and the decrease of fibrinogen (P<0.05) suggested the development of disseminated intravascular coagulation (DIC), induced by activated endothelium and intensified by transient hepatic failure. We concluded that activation of the endothelium mediated by IL-2 was accompanied by a loss of endothelial integrity and capillary leak. The activated endothelium can trigger DIC via activation of the coagulation cascade. The increased ET-1 might act as an endogenous counter-regulator of the disadvantageous haemodynamic side-effects induced by IL-2.

Blood Coagulation↗
PubMed1999

Circadian variation of granulocyte colony stimulating factor levels in man.

Glucocorticoids dose-dependently increase plasma levels of granulocyte colony stimulating factor (G-CSF). Based on the marked circadian rhythm of cortisol levels, we hypothesized that plasma levels of G-CSF may also show a diurnal rhythm. A prospective study was conducted in 12 healthy young volunteers. Blood samples were obtained every 2 h over 24 h. G-CSF levels averaged 18.0 ng/l (CI 13. 1-22.9) at 8.00 am, increased continuously and reached peak values at 10.00 p.m. Individual harmonic regression analysis showed a clear circadian rhythm. The individual differences between nadir and peak levels averaged 54% (CI 43-65%). This pronounced diurnal rhythm of G-CSF levels may help understand the circadian changes in circulating stem cells, bone marrow DNA synthesis, or bone marrow toxicity induced by some chemotherapeutic agents.

Adult↗
PubMed1999

Regulation of adhesion molecules during human endotoxemia. No acute effects of aspirin.

Gram-negative septic shock is mediated in part by endotoxin (lipopolysaccharide; LPS), and animal models have shown that blockade of even single adhesion molecules considerably improves survival. Thus interference with the adhesion cascade may provide a useful therapeutic approach in human sepsis. Young healthy men (n = 30) each received a bolus of 4 ng/kg LPS intravenously to study the effects of endotoxemia on adhesion processes in humans and to identify potential targets for pharmacologic intervention. One third of subjects received pretreatment with 1,000 mg aspirin and 1,000 mg paracetamol to study potential antiinflammatory effects of aspirin or effects of antipyresis. Circulating neutrophils dropped by -80% at 67 min after LPS, monocytes by -96% at 90 min, and lymphocytes by -85% at 240 min. L-selectin expression decreased, particularly on monocytes. Circulating (c)E-selectin levels increased by 820%, von Willebrand factor-Ag (vWF), soluble thrombomodulin, circulating (c)P-selectin, circulating intercellular adhesion molecule-1 (cICAM-1), and circulating vascular cell adhesion molecule-1 (cVCAM-1) by a mean of 65 to 98% (p < 0.001 for all), but cL-selectin by only 15%. Urinary excretion of soluble adhesion molecules was negligible. Aspirin had no influence on the LPS-induced changes of adhesion parameters, but paracetamol blunted the relative increase in vWF while having no effects on the other parameters measured. The consistent, profound, and early upregulation of cE-selectin during endotoxemia indicates that cE-selectin may be a better surrogate marker to monitor the activation status of endothelial cells in systemic inflammation than the other markers measured. Although aspirin did not have any antiinflammatory effects in this model, paracetamol lowered the relative increase in vWF.

Acetaminophen↗
PubMed1997

Dexamethasone down-regulates the expression of L-selectin on the surface of neutrophils and lymphocytes in humans.

OBJECTIVE: On the basis of previous animal studies, we hypothesized that dexamethasone may reduce the expression of L-selectin on neutrophils and lymphocytes in healthy men. METHODS: A double-blind, randomized, placebo-controlled, and three-way crossover trial was conducted in nine healthy men. Every subject received four identical infusions of saline solution, 0.04 mg/kg dexamethasone, or 1.0 mg/kg dexamethasone during three observation periods of 48 hours each. RESULTS: Dexamethasone time and dose dependently decreased the L-selectin expression on neutrophils and lymphocytes as measured by flowcytometry. This effect occurred with a time lag of 8 hours after start of treatment: the L-selectin binding index of neutrophils decreased by a maximum of -50% (confidence interval [CI], -37% to -63%) and that of lymphocytes by -26% (CI, -8% to -45%) at 32 hours after the start of treatment with high-dose dexamethasone (p < 0.016). Low-dose dexamethasone had only a transient effect on L-selectin expression of lymphocytes and a less pronounced effect on L-selectin expression of neutrophils. CONCLUSION: Dexamethasone time and dose dependently decreases L-selectin expression on neutrophils and lymphocytes in health men, an effect that is less pronounced than that previously reported for animals.

Adult↗
PubMed1997

Menstrual cycle-associated changes in blood levels of interleukin-6, alpha1 acid glycoprotein, and C-reactive protein.

Based on previous studies we hypothesized that interleukin-6 (IL-6) plasma levels would increase during the menstrual cycle, in analogy to the increase in IL-1 levels seen during the luteal phase. Thus we have investigated menstrual cycle-associated changes in IL-6, alpha1 acid glycoprotein (AGP), and C-reactive protein (CRP). The study design was cross-sectional and was conducted in 18 healthy premenopausal women with regular menstrual cycles and in 15 age-matched men. The women had blood drawings in the follicular phase, at midcycle, and in the luteal phase of the menstrual cycle. A single blood sample was obtained from men to compare IL-6 levels between sexes. The median IL-6 level was 0.68 pg/ml (95% confidence interval (CI): 0.60 to 1.05) in the follicular phase and did not change significantly during the menstrual cycle. IL-6 levels did not differ between women and men (0.79 pg/ml; CI: 0.66 to 1.05; p > 0.05). Median AGP levels decreased by 6% (CI: -14% to 1%) during the luteal phase (p = 0.005), and a significant correlation between mean AGP and IL-6 levels was found (r = 0.60; p = 0.01). Median CRP levels increased by 44% (CI: 27% to 59%; p < 0.001) at midcycle and by 31% (CI: 17% to 68%; p = 0.002) in the luteal phase, and there was a significant correlation between the relative increase in CRP at midcycle and the relative increase in progesterone levels during midcycle (r = 0.60; p = 0.01) and the luteal phase (r = 0.71; p = 0.001). In conclusion, we found no sustained menstrual cycle-dependent changes in systemic IL-6 plasma levels. AGP and CRP levels may be differentially regulated during the menstrual cycle of healthy women: AGP levels correlated with IL-6 levels, and AGP levels decreased during the menstrual cycle, whereas CRP levels increased during the menstrual cycle and correlated with the increase in progesterone levels. The reason for the observed changes in CRP levels remains to be elucidated.

Adult↗
PubMed1997

Effects of angiotensin-II infusion at pressor and subpressor doses on endothelin-1 plasma levels in healthy men.

Several lines of evidence suggest that effects of angiotensin-II (A-II) could be mediated in part by endothelin-1 (ET-1): A-II enhances production and secretion of ET-1 which in turn may contribute to the pressor effects and mitogenic actions of A-II. We have conducted a randomized controlled cross-over study to investigate whether A-II increases ET-1 plasma levels in humans at pressor doses. Each of the eight healthy male volunteers received a subpressor and pressor dose of A-II which were assessed by titration of the individual dose dependent blood pressure responses to A-II-infusion. The mean subpressor dose of A-II was 0.62 ng/kg/min. (range: 0.31-1.25); the mean pressor dose of A-II was 8.44 ng/kg/min. (range 2.5-20), yielding an average increase in mean arterial pressure by 35% (95% confidence interval [CI]: 24-45%). Plasma ET-1 concentrations increased significantly only in response to pressor doses of A-II (Friedman ANOVA p=0.022): ET-1 increased by 89 % (CI: 24-154%) over baseline (1.7 pmol/L; CI: 1.4-2.0) 60 min. after starting the pressor infusion of A-II and remained elevated throughout the 4-hours observation period. In conclusion, A-II at pressor doses but not at subpressor doses induced an increase in plasma levels of ET- 1 in healthy subjects. This finding may be of relevance for various diseases associated with increased production of A-II and could potentially have therapeutic implications.

Adult↗
PubMed1997

Effects of exercise on circulating vascular adhesion molecules in healthy men.

Based on previous studies showing an increase in circulating soluble intercellular adhesion molecule-1 (sICAM-1) after exercise, we hypothesized that exercise may also increase serum levels of the vascular cell adhesion molecule-1 (sVCAM-1) and sE-selection. In a prospective controlled clinical trial, serum levels of sE-selectin, sICAM-1 and sVAM-1 were measured before and after two different exercise protocols in healthy untrained men. Lactate levels increased up to 12.7 mmol/L (95% confidence interval: 10.1-15.9) and 3.6 mmol/L (CI: 2.4-4.7) after ergometry and after an one hour endurance exercise at 60% of the maximal work intensity, respectively (p = 0.028 vs baseline and controls). The maximal increase in lymphocyte counts of 106% (CI: 63-146), which was only of short duration, was higher immediately after ergometry as compared to that observed after endurance exercise (p = 0.028). However, the maximal increase in neutrophil counts of 178% (CI: 120-298) which was seen at 2 hours after endurance exercise was higher than that seen after ergometry (p = 0.028). In contrast, only small changes of circulating adhesion molecules were seen immediately after ergometry: sICAM-1 increased by 11% (CI: 4-25; p = 0.028), and similar tendencies were also observed for sVCAM-1 and sE-selectin. No other consistent and time-dependent changes of circulating adhesion molecules were observed and all differences and changes were < or = 11%. In sum our study provides evidence that recreational sporting activities in untrained healthy subjects at normal altitude have little influence on serum levels of the circulating vascular adhesion molecules sE-selectin, sVCAM-1 or sICAM-1.

Adult↗