Association of folate transporter SLC19A1 polymorphisms with the outcome of multiple myeloma after chemotherapy and tandem autologous transplantation.
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Aged↗
Biomedical subjects
N Giuliani
Publications and source records attributed to N Giuliani.
Human myeloma cells express the bone regulating gene Runx2/Cbfa1 and produce osteopontin that is involved in angiogenesis in multiple myeloma patients.
Osteopontin (OPN) is a multifunctional bone matrix glycoprotein that is involved in angiogenesis, cell survival and tumor progression. In this study we show that human myeloma cells directly produce OPN and express its major regulating gene Runx2/Cbfa1. The activity of Runx2/Cbfa1 protein in human myeloma cells has also been demonstrated. Moreover, using small interfering RNA (siRNA) to silent Runx2 in myeloma cells, we suppressed OPN mRNA and protein expression. OPN production in myeloma cells was stimulated by growth factors as IL-6 and IFG-1 and in turn OPN stimulated myeloma cell proliferation. In an 'in vitro' angiogenesis system we showed that OPN production by myeloma cells is critical for the proangiogenic effect of myeloma cells. The expression of OPN by purified bone marrow (BM) CD138(+) cells has also been investigated in 60 newly diagnosed multiple myeloma (MM) patients, finding that 40% of MM patients tested expressed OPN. Higher OPN levels have been detected in the BM plasma of MM patients positive for OPN as compared to controls. Moreover, significantly higher BM angiogenesis has been observed in MM patients positive for OPN as compared to those negative. Our data highlight that human myeloma cells with active Runx2/Cbfa1 protein directly produce OPN that is involved in the pathophysiology of MM-induced angiogenesis.
Bone Marrow↗
Downmodulation of ERK protein kinase activity inhibits VEGF secretion by human myeloma cells and myeloma-induced angiogenesis.
The mitogen-activated protein (MAP) cascade leading to the activation of extracellular signal-regulated kinases 1/2 (ERK1/2) is critical for regulating myeloma cell growth; however, the relationship of ERK1/2 activity with vascular endothelial growth factor (VEGF) production and the effects of its downmodulation in myeloma cells are not elucidated. We found that the treatment with MAP/ERK kinase 1 (MEK1) inhibitors PD98059 or PD184352 produced a reduction of phosphorylated ERK1/2 (p-ERK1/2) levels in myeloma cells of more than 80% and prevented the increase of p-ERK1/2 induced by interleukin-6 (IL-6). MEK1 inhibitors also induced a significant inhibition of myeloma cell proliferation and blunted the stimulatory effect induced by IL-6. A significant inhibition of basal VEGF secretion by myeloma cells as well as a suppression of the stimulatory effect of IL-6 on VEGF was observed by either PD98059 or PD184352. Moreover, we also found that the PI3K kinase inhibitors, but not p38 MAPK inhibitors, reduced VEGF secretion by myeloma cells and increase the inhibitory effect of MEK1 inhibitors. In an 'in vitro' model of angiogenesis, we found that MEK1 inhibitors impair vessel formation induced by myeloma cells and restored by VEGF treatment, suggesting that the downmodulation of ERK1/2 activity reduces myeloma-induced angiogenesis by inhibiting VEGF secretion.
Cell Division↗
Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment.
Although osteolysis is a common complication in patients with multiple myeloma (MM), the biologic mechanisms involved in the pathogenesis of MM-induced bone disease are poorly understood. Two factors produced by stromal-osteoblastic cells seem critical to the regulation of bone resorption: osteoprotegerin (OPG) and its ligand (OPGL). OPGL stimulates osteoclast differentiation and activity, whereas OPG inhibits these processes. The present study investigated whether myeloma cells affect physiologic OPG/OPGL balance in the bone marrow (BM) environment. Ten human myeloma cell lines and myeloma cells isolated from 26 consecutive patients with MM failed to express OPGL and only rarely produced a low amount of OPG. In a coculture system, human myeloma cells up-regulated OPGL expression but strongly down-regulated OPG production in preosteoblastic (preOB) or stromal cells (BMSCs) of primary human BM at the mRNA and protein levels. This effect, which was dependent on cell-to-cell contact between myeloma cells and BMSCs or preOB, partially involved the integrin VLA-4. In addition, overexpression of OPGL mRNA occurred in ex vivo BM cultures obtained from MM patients as compared with healthy donors, and immunohistochemical staining performed on BM biopsy specimens showed an increase of OPGL and a reduction of OPG expression in MM patients as compared with healthy subjects. In summary, these data indicate that myeloma cells affect the OPG/OPGL ratio in the BM environment and tend to confirm that the OPG/OPGL system is involved in the pathogenesis of MM-induced bone disease.
Aged↗
Serum interleukin-6, soluble interleukin-6 receptor and soluble gp130 exhibit different patterns of age- and menopause-related changes.
Growing evidence suggests that interleukin-6 (IL-6) may play a pathogenetic role in postmenopausal bone loss and in other age-related pathological conditions. In this study, we have examined the age-related changes in the serum levels of IL-6 and the soluble receptors that modulate its biological activity--soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130)--in 220 women (from 25 to 104yr old), including 22 centenarians. Serum IL-6 rose exponentially with age (r=0.74, p<0.0001). The median level of IL-6 increased almost ten-fold with age, from 1.16pg/ml in premenopausal women to 10.27pg/ml in centenarians. Serum sIL-6R and sgp130 showed an increase until the seventh decade and a progressive decrease in older ages (r=0.39, p<0.0001 and r=0.26, p=0.008, respectively). IL-6, sIL-6R and sgp130 were significantly higher in women within 10yr of menopause as compared to premenopausal subjects (1.51 vs. 1.16pg/ml, p=0.012; 41.9 vs. 35.7ng/ml, p=0.002; and 253.4 vs. 230.7ng/ml, p=0.008, respectively). In postmenopausal women, a negative correlation was found between sIL-6R and the lumbar bone mineral density (BMD) (r=-0.28, p=0.002) even after adjusting for age and weight. Furthermore, sIL-6R levels were higher in osteoporotic compared to normal women (47.9 vs. 39.5ng/ml, p=0.001). In conclusion, our results show that the serum levels of IL-6, sIL-6R and sgp130 exhibit different patterns of age- and menopause-related changes, and that the biological activity of IL-6 may be increased with age with potential implications in the age-related diseases such as osteoporosis.
Adult↗
Serum concentrations of proinflammatory cytokines in Graves' disease: effect of treatment, thyroid function, ophthalmopathy and cigarette smoking.
OBJECTIVE: In the present study we have measured the concentrations of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-1 receptor antagonist (IL-1Ra) in the serum of patients with Graves' disease (GD). By multivariate analysis, we have evaluated the effect of antithyroid treatment, thyroid function, the presence or absence of active thyroid-associated ophthalmopathy (TAO), the patient's smoking habits and the relation to circulating anti-thyrotropin (TSH) receptor (TRAb) and anti-thyroperoxidase antibodies (TPOAb). SUBJECTS: We studied 84 GD patients, 51 untreated and 33 receiving methimazole (MMI) therapy. Twenty-three (45%) untreated patients and 18 (54%) patients on MMI had active TAO. We also studied 67 normal subjects as controls. Thirty-one GD patients (43%) and 16 controls (36%) were smokers. RESULTS: Serum IL-6 concentrations were significantly higher in both untreated patients (P<0.001) and treated patients (P<0.006), when compared with controls. Serum sIL-6R concentrations were significantly affected by treatment (P=0.001). Serum IL-1Ra concentrations were not different in GD patients, whether treated or untreated, compared with controls. Serum IL-6 concentrations were not influenced by thyroid function and there was a significant interaction between treatment and the presence of active TAO (P=0.003). In hyperthyroid patients with active TAO serum, sIL-6R concentrations were significantly higher than in those with inactive TAO (P=0.003). In untreated GD patients there was no significant effect of thyroid function and TAO activity on the serum concentrations of TNF-alpha and IL-1 beta. Serum IL-1Ra concentrations were not affected by the presence of TAO. Smoking had no effect on serum IL-6, sIL-6R, TNF-alpha, IL-1 beta and IL-1Ra concentrations, even in the presence of an active TAO. Serum concentrations of IL-6, sIL-6R, TNF-alpha and IL-1 beta and IL-1Ra were not different in patients with and without TRAb or TPOAb, in relation to either thyroid function, TAO activity or smoking. CONCLUSIONS: Our work shows that: (i) the proinflammatory cytokine pattern in GD is greatly influenced by antithyroid drug treatment; (ii) the increased circulating IL-6/sIL-6R concentrations observed in patients with active TAO may derive from the activation of humoral reactions in sites other than the thyroid; and, (iii) cigarette smoking has no effect on serum IL-1/IL-1Ra concentrations in TAO.
Adolescent↗
The use of frozen-thawed platelet-derived phospholipids as a confirmatory test for the diagnosis of lupus anticoagulants. Comparison with two commercial confirmatory system tests.
Lupus anticoagulants (LAs) belong to acquired circulating anticoagulants interfering with phospholipid-dependent coagulation tests. Owing to the remarkable variability among patients, SSC guidelines recommend more than one test to detect and confirm the presence of LAs. However, this is an expensive procedure and greatly raises the work load of the laboratory. A standardised platelet-derived phospholipid preparation was obtained and platelet neutralisation (PNP) procedures with APTT and DRVVT reagents were performed on plasmas from 16 patients with LAs and from 41 control subjects. In comparisons, STAclot-PNP and DVVconfirm clotting assays were conducted. PNP by using APTT or DRVVT reagents showed intra-assay coefficient of variation of 1.6 and 1.8%, whereas inter-assays coefficient of variations were 6.8 and 5.1%, respectively. A complete concordance was achieved between STAclot-PNP and PNP by using APTT reagents and between DVV-confirm and PNP with DRVVT reagents, demonstrating a high reliability of both the PNP-based assays. This consistency indicates that the standardised platelet-derived phospholipid preparation obtained allows for reliable, reproducible, and cheap PNP-based confirmatory assays for LAs testing.
Adolescent↗
Oestrogens prevent the increase of human serum soluble interleukin-6 receptor induced by ovariectomy in vivo and decrease its release in human osteoblastic cells in vitro.
OBJECTIVE: Interleukin-6 (IL-6) seems to be a key mediator of the increased bone loss that follows loss of ovarian function. Based on this and on evidence that oestrogen deficiency may also increase cell sensitivity to IL-6, we studied the effects of ovariectomy and of oestrogen replacement therapy on the serum levels of IL-6 and of soluble IL-6 receptor (sIL-6R) in vivo. DESIGN AND PATIENTS: Thirty-seven fertile women undergoing surgery for benign uterine diseases were divided into 3 groups and monitored for 12 months: hysterectomized women (n = 9), ovariectomized untreated women (n = 12) and ovariectomized women starting treatment with transdermal estradiol (E2, 50 microg/d) 1 month after surgery (n = 16). RESULTS: Hysterectomy alone caused no significant changes of sIL6R whereas serum levels of sIL-6R rose progressively after ovariectomy (mean +/- SEM: 31 +/- 9% and 38 +/- 7% over baseline, at 6 and 12 months, respectively; P < 0.01). Oestrogen replacement therapy prevented the increase of sIL6R over a 1-year period. A similar pattern was also found for serum IL-6 but the changes did not reach statistical significance. In ovariectomized (OVX) women there were significant correlations between serum sIL-6R levels and FSH (r = 0.59; P < 0. 01), oestradiol (r = - 0.43; P < 0.01), testosterone (r = - 0.41; P < 0.05), osteocalcin (r = 0.42; P < 0.05) and bone alkaline phosphatase (r = 0.44; P < 0.05). To examine whether oestrogen directly regulates sIL-6R secretion by bone cells, we studied in vitro the basal and phorbol ester (PMA) stimulated release of sIL-6R in a human osteoblastic cell-line (MG-63) and in a tumour-derived osteoclastic cell line (GCT-51). Osteoblastic (but not osteoclastic) cells spontaneously produced considerable amounts of sIL-6R and the protein kinase-C activator PMA (10-8 M) increased the release of sIL-6R by osteoblasts more than 3-fold. More strikingly, 17beta E2 (but not 17alpha) significantly inhibited both the spontaneous- and PMA-induced release of sIL-6R by osteoblastic cells (P < 0.05). CONCLUSIONS: These results indicate that oestrogen loss causes alterations of the IL-6 system, and that sIL-6R is under the direct inhibitory control of oestrogens both in vivo and in vitro.
Alkaline Phosphatase↗
Inherited prothrombotic conditions and premature ischemic stroke: sex difference in the association with factor V Leiden.
At a young age, ischemic stroke is an uncommon event in which prothrombotic factors are likely to play an important role. In 202 referred cases, 105 men and 97 women, median age 39 years (range, 3 to 50), with a history of ischemic stroke and in 1036 age frequency-matched apparently healthy individuals from the same ethnic background, we have investigated whether inherited prothrombotic conditions increase the risk of ischemic stroke. Neither abnormal plasma levels of natural anticoagulants and fibrinogen nor significant increase of the prothrombin A20210 allele was found in stroke cases compared with controls. Hypertension (odds ratio [OR], 22.61), male sex (OR, 2.30), smoking (OR, 2.78) and alcohol habits (OR, 0.14), a personal history of venous thromboembolism (OR, 4.53), a family history of stroke (OR, 1.93), high circulating levels of fibrinogen (P=0.0190), and total cholesterol (P=0.101) were all independently associated with ischemic stroke. Compared with noncarriers, carriers of the factor V (FV) Leiden mutation (OR, 2.56), and to a lesser extent, of the methylenetetrahydrofolate reductase (MTHFR) TT genotype (OR, 1.60), had an independent higher estimated risk of having a history of ischemic stroke. The relationship with the FV Leiden mutation was greater in women (OR, 3.95). Thus, in addition to established determinants, FV Leiden mutation is independently associated with the occurrence of ischemic stroke in this setting. The greater association in women suggests the possibility of an interaction of this genotype with female hormones.
Adolescent↗
Ethanol and acetaldehyde inhibit the formation of early osteoblast progenitors in murine and human bone marrow cultures.
Alcohol abuse is commonly associated with reduced bone mass and osteoporosis as a consequence of both systemic and direct cellular effects. To clarify some of the pathways by which alcohol exerts its actions directly on bone cells, we investigated the formation of early osteoblast progenitors (colony-forming units for fibroblasts; CFU-F) in long-term murine and human bone marrow cultures exposed to ethanol and to its main metabolite, acetaldehyde. In murine bone marrow cultures, obtained from Swiss female mice, ethanol inhibited CFU-F formation (maximal reduction +/- SEM: 50 +/- 2%; p < 0.01) at concentrations ranging from 0.04% to 0.6% that are similar to those reached in vivo in alcoholics. Acetaldehyde strongly reduced CFU-F formation at concentrations of 0.004% and 0.02%, and completely abolished it at the dose of 0.06%. Similarly, ethanol (at concentrations > or =0.02%) and acetaldehyde (from 0.004% to 0.06%) significantly decreased the number of CFU-F in human bone marrow cultures; the mean reduction observed with ethanol was 63 +/- 12% (p < 0.05), whereas acetaldehyde completely prevented CFU-F formation at the concentration of 0.06%. These in vitro observations were confirmed by the in vivo findings that the CFU-F formation in bone marrow cultures from nine young, chronic, noncirrhotic alcoholics was significantly reduced (70 +/- 15%), compared with seven age-matched normal subjects (p < 0.01). In addition, acetaldehyde inhibited cell proliferation in human osteoblastic cells (MG-63 and HOBIT cell lines), whereas ethanol reduced proliferation only in MG-63 cells. Our results indicate that ethanol and acetaldehyde may directly inhibit the osteoblastogenic potential of the bone marrow, and this effect may contribute to the decreased bone formation observed in alcoholics.
Acetaldehyde↗
Increased risk for venous thrombosis in carriers of the prothrombin G-->A20210 gene variant.
BACKGROUND: A mutation in the prothrombin gene (G-->A20210) has been associated with higher plasma prothrombin levels and an increased tendency for venous thrombosis. OBJECTIVE: To determine whether the prothrombin A20210 allele is independently associated with the occurrence of venous thrombosis. DESIGN: Case-control study. SETTING: Two thrombosis centers in southern Italy. PATIENTS: 281 consecutive patients with venous thrombosis confirmed by objective tests and 850 controls. MEASUREMENTS: Medical history was collected on standardized questionnaires. The presence of prothrombin G-->A2020 and factor V Leiden mutations was determined by polymerase chain reaction. The presence of anticoagulant factors and prothrombin activity was determined by tests of function. RESULTS: In 150 controls, increased prothrombin activity (P < 0.001) was associated with the prothrombin A20210 allele. This allele was more frequent in patients than in controls (8.01% compared with 2.29%; P < 0.001) and was associated with an increased risk for thrombosis (odds ratio, 3.88 [95% CI, 2.23 to 6.74]). The increased prevalence of this allele was independent of the presence of the factor V Leiden mutation. After adjustment for sex, age, arterial thrombosis, and factor V Leiden mutation, the risk was still significantly elevated (odds ratio, 3.13 [CI, 1.89 to 5.21]). Moreover, the overall prevalence of inherited coagulation abnormalities was significantly higher in patients with thrombosis of the lower extremities than in patients with thrombosis of the upper extremities (odds ratio, 3.77 [CI, 1.10 to 12.93]). Fourteen patients carried both the prothrombin G-->A20210 and factor V Leiden mutations. CONCLUSIONS: The prothrombin A20210 allele is independently associated with the occurrence of venous thrombosis, particularly in patients with a history of thrombosis of the lower extremities.
Adolescent↗
Stimulation of ACTH and GH release by angiotensin II in normal men is mediated by the AT1 receptor subtype.
This study was performed in order to determine whether the stimulatory effect of plasma angiotensin II (ANG II) on Adrenocorticotropic hormone (ACTH) and growth hormone (GH) secretion in humans is mediated by AT1 subtype receptors. For this purpose, the effects of the administration of the AT1 receptor antagonist, losartan (50 mg p.o.) or a placebo on the ACTH and GH responses to ANG II (i.v. infusion for 60 min of successively increasing doses (4, 8 and 16 ng/kg/min); each dose for 20 min) were evaluated in eight normal men. ANG II infusion induced significant increases in both serum ACTH and GH levels (mean peaks were 1.6- and four-times higher than baseline, respectively). The ACTH response to ANG II was completely abolished by pretreatment with losartan. Also, the ANG II-induced GH rise was reduced by administration of losartan, but the GH response was still significantly higher than the basal value (mean peak was twice as high as the baseline). These data provide evidence of AT1 receptor involvement in mediation of the ANG-II stimulating effect on ACTH and GH secretion.
Adrenocorticotropic Hormone↗
Identifying human platelet glycoproteins IIb and IIIa by capillary electrophoresis.
Glanzmann thrombasthenia (GT) is an inherited hemorrhagic defect due to a failure of the platelet membrane glycoprotein (GP) IIb-IIIa complex. Capillary electrophoresis (CE) analysis of solubilized platelet membranes from normal individuals showed the presence of two peaks with a migration time of 27 and 29 min, respectively. An excellent run-to-run and day-to-day reproducibility of the technique (< 1% variation of the retention time) was documented. Using an automated Ferguson method, the apparent molecular masses were 100.0 kDa and 138.5 kDa, respectively. Immunoprecipitation with monoclonal antibodies anti-GP IIIa (B59.2.1) and anti-IIb (61.9.1.3) showed the two peaks as IIIa and IIb, respectively. Electropherograms of a GT young man showed the lack of both peaks. Less than 50% of each peak was present in his parents. Polyacrylamide gel electrophoresis (PAGE), immunoblotting, and flow cytometry analyses showed that GP IIb and IIIa were undetectable in the platelet membranes from the propositus, half of the normal amount being present in both parents. These findings indicate CE to be a rapid, sensitive and reliable tool to investigate patients with abnormalities of the GP IIb-IIIa complex.
Blood Platelets↗
5-HT3 serotonergic receptor mediation of hypoglycemia-induced arginine-vasopressin but not oxytocin secretion in normal men.
The present study was undertaken in order to establish the possible involvement of 5-HT3 serotonergic receptors in the control of basal and/or hypoglycemia-stimulated arginine vasopressin (AVP) and/or oxytocin (OT) secretion. For this purpose, 12 normal men were injected intravenously with a bolus of 4 mg ondansetron, a specific 5-HT3 receptor antagonist, under basal conditions (n = 6) or 30 min before insulin (0.15 IU/kg body weight) administration (n = 6) (insulin tolerance test (ITT)). Control experiments with normal saline instead of ondansetron treatment were performed. Furthermore, on a different occasion, the same subjects were tested in identical experimental conditions with 8 mg ondansetron. Our results showed that the hypoglycemic response to insulin was similar during the ITT and ondansetron plus ITT. Inhibition of 5-HT3 serotonergic receptors with ondansetron (4 or 8 mg) did not modify the basal secretion of AVP and OT and the OT response to insulin-induced hypoglycemia. In contrast, the administration of 4 or 8 mg ondansetron significantly reduced in a similar manner hypoglycemia-induced AVP rise. Mean peak level at 45 min after insulin injection was 2.25 times higher than baseline in the control ITT and 1.5 times higher than basal value in the ondansetron (4 or 8 mg) plus ITT. These data demonstrate that 5-HT3 serotonergic receptors at least partially mediate the AVP response to hypoglycemia, without modifying the simultaneous OT response. On the other hand, 5-HT3 receptors do not appear to be involved in the control of basal posterior pituitary hormone secretions.
Adult↗
Melatonin inhibits oxytocin response to insulin-induced hypoglycemia, but not to angiotensin II in normal men.
In order to establish whether melatonin alters basal and/or stimulated oxytocin secretion, 18 normal men were treated (p.o.) with 6 or 12 mg melatonin or placebo in basal conditions (N-6 subjects) or concomitantly to the administration of insulin (O.15 IU/kg body weight in an i.v. bolus) (N-6 subjects) or angiotensin II (increasing doses of 4, 8 and 16 ng/kg/min, at intervals of 20 min). The administration of 6 or 12 mg melatonin did not change basal and angiotensin II-stimulated oxytocin secretion. In contrast, the oxytocin response to insulin-induced hypoglycemia was significantly reduced by melatonin treatment. In fact, the mean peak oxytocin response to hypoglycemia was 2.2 times higher than baseline in the absence of melatonin, whereas it was 1.6 times higher than basal value after administration of 6 or 12 mg melatonin. These data indicate an involvement of melatonin in the regulation of the oxytocin response to hypoglycemia in normal men. The lack of effects of melatonin on basal and angiotensin II-stimulated oxytocin secretion argues against the possibility that melatonin exerts an overall modulatory role on oxytocin secretion in humans.
Adult↗
Different effects of naloxone on the growth hormone response to melatonin and pyridostigmine in normal men.
The effect of melatonin (MEL) (12 mg orally), pyridostigmine (60 mg orally), the combination of MEL and pyridostigmine, or placebo on growth hormone (GH) secretion was tested in seven normal men. In addition, MEL tests and pyridostigmine tests were repeated after pretreatment with naloxone (1.2-mg bolus followed by intravenous [i.v.] infusion of 1.6 mg/h for 3 hours). Serum GH levels increased fivefold after MEL and sixfold after pyridostigmine administration. The concomitant administration of MEL did not change the GH response to pyridostigmine. In the presence of naloxone, the GH response to MEL was completely abolished, whereas naloxone did not modify the pyridostigmine-induced GH increase. These data suggest that MEL and pyridostigmine stimulate GH secretion through a common mechanism, which is probably represented by the inhibition of somatostatin activity. However, in contrast to pyridostigmine, the action of MEL appears to be exerted through a naloxone-sensitive opioid mediation.
Administration, Oral↗
Arginine vasopressin and oxytocin responses to angiotensin II are mediated by AT1 receptor subtype in normal men.
This study was performed to determine whether the stimulatory effect of plasma angiotensin II (ANG II) on arginine vasopressin (AVP) and oxytocin (OT) secretion in humans is mediated by AT1 subtype receptors. For this purpose, the effects of the AT1 receptor antagonist losartan (50 mg orally) or a placebo on the AVP and OT responses to ANG II (intravenous infusion for 60 minutes of successively increasing doses of 4, 8, and 16 ng/kg min; each dose for 20 minutes) administration were evaluated in seven normal men. In additional experiments, the same subjects were tested with losartan (50 mg orally) alone or placebo alone. Neither losartan nor placebo given alone modified the basal levels of AVP and OT. ANG II infusion induced significant increments in both serum AVP and OT levels (mean peaks were 1.55 and 1.41 times higher than baseline, respectively). Both hormonal responses to ANG II were completely abolished by pretreatment with losartan. These data provide evidence of AT1 receptor involvement in mediation of the ANG II-stimulating effect on AVP and OT secretion.
Adult↗
Effect of melatonin on arginine vasopressin secretion stimulated by physical exercise or angiotensin II in normal men.
The present study was undertaken in order to establish the possible involvement of melatonin in the mechanisms underlying the arginine-vasopressin (AVP) responses to physical exercise and angiotensin II (ANG II). On two mornings at least 1 week apart, normal male subjects were tested with exercise on a bicycle ergometer (the workload was gradually increased at 3-min intervals until exhaustion and lasted about 15 min in all subjects) or ANG II (60-min infusion of ANG II (Asp 1, IIe 5 angiotensin II) dissolved in 5% glucose in successively increasing doses of 4, 8, 16 ng/kg/min; each dose for 20 min). Tests were carried out with the administration of either 6 mg melatonin or placebo. Melatonin treatment neither modified the basal concentrations of AVP nor changed the AVP response to ANG II. In contrast, plasma AVP levels rose 3.6 times during exercise in the absence of melatonin, but only 2.3 times in the presence of melatonin. These data indicate an involvement of melatonin in the mechanism underlying the AVP response to physical exercise, but not ANG II, in normal men.
Adult↗