Bone morphogenetic protein-2 may represent the molecular link between oxidative stress and vascular stiffness in chronic kidney disease.

Oxidative stress and vascular calcifications are emergent risk factors for the accelerated atherosclerosis process featuring chronic kidney disease (CKD). Vascular calcification is an active process similar to bone modelling, where BMP-2 may play a pathogenic role. Aim of our study was to investigate the link between oxidative stress, BMP-2 protein expression and vascular disease in CKD. We enrolled 85 CKD patients (K-DOQI stage II or higher) and 41 healthy individuals. 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG) was used as a marker of oxidative stress. Brachial-ankle pulse wave velocity (baPWV) was used as a measure of arterial stiffness. BMP-2 serum levels were significantly higher in CKD patients than in controls (p<0.0001). Serum 8-OHdG levels were significantly higher in CKD patients compared to controls (p<0.05). BMP-2 serum levels were inversely associated with eGFR (r=-0.3; p=0.01) and directly correlated with 8-OHdG serum concentrations (r=-0.3; p=0.03). Arterial stiffness was inversely correlated with eGFR (r=-0.4; p=0.001) and directly correlated with BMP-2 (r=0.3; p=0.03), 8-OHdG (r=0.4, p=0.02) and phosphorus serum levels (r=0.3; p=0.007). In a multiple regression model, phosphorus and BMP-2 were independently correlated with baPWV. In vitro exposure to H(2)O(2) induced a time and dose-dependent increase in BMP-2 expression in an immortalized endothelial cell line. Moreover, H(2)O(2) pre-incubation of cultured vascular smooth muscle cell enhanced the BMP-2-induced up-regulation of ALPL, an osteoblastic phenotype marker. Our data suggest that in CKD BMP-2 may represent the molecular link between oxidative stress and arterial stiffness due to vascular calcification.

Effects of rosiglitazone, a PPAR-gamma agonist, on the contractility of bovine uterus in vitro.

Rosiglitazone is a drug used in human medicine for treating type II diabetes mellitus. It activates Peroxisome Proliferators-Activated Receptors gamma (PPAR-gamma), which regulate energetic metabolism. We aimed to evaluate the effects of rosiglitazone on bovine myometrial contractility in vitro. Myometrial strips were collected from uteri of cows in estrus, diestrus, and pregnancy. Contractions were recorded using an isometric force transducer. After the equilibration period, rosiglitazone (1 x 10(-6)) was added to the bath. Its effects on the amplitude and frequency of spontaneous contractions were evaluated. Data were analyzed using an ANOVA and Student's t-test and were considered significant at P < 0.05. Rosiglitazone increased the mean amplitude during estrus (P < 0.01), diestrus (P < 0.05), and pregnancy (P < 0.01); the frequency of contractions in both pregnancy (P < 0.05) and diestrus (P < 0.05) increased as well. These effects are likely due, in our opinion, to an increase in intracellular calcium concentrations, as well as enhanced uptake of glucose from the Krebs' solution. The differences observed according in the different phases are ascribable to the different hormonal milieu. Our study indicates that rosiglitazone affects bovine myometrial contractility. It may be considered a starting point for further studies on the application of this drug in veterinary obstetrics.

Opioid agonist/antagonist effect of naloxone in modulating rabbit jejunum contractility in vitro.

Opioid peptides are the most effective drugs in controlling pain; their action is elicited by binding to specific membrane receptors. The gastrointestinal tract represents, after the nervous system, the site in which the opioid receptors are expressed at high levels. The opioid agonist morphine has a significant inhibitory effect on intestinal motility, this action is blocked by naloxone an opioid antagonist mainly active at mu and kappa receptors. In this study the presence of mu opioid receptor on rabbit jejunum was investigated by western blot. The effects of beta-endorphin, the endogenous opioid peptide with the highest affinity to the mu opioid receptor and those of naloxone on spontaneous rabbit jejunum contractions were evaluated. Beta-endorphin (10(-6) M) showed a relaxant effect on jejunum contractility while naloxone showed a dual effect inducing an increase of spontaneous contractility at low concentrations (10(-6) M, 10(-7) M, 10(-8) M) and a decrease when high concentrations (10(-3) M, 10(-4) M, 10(-5) M) were utilized. The obtained results demonstrate that mu opioid receptor is expressed in rabbit jejunum and suggest that this receptor may be involved in mediating the effects of both opioid agonist and antagonist on jejunum contractions.