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Aims The influence of blood flow disturbances on vascular function, endothelial activation and repair capacity has not been fully elucidated either in physiological conditions or in cardiovascular disease. We aimed to determine the impact of increases in retrograde blood flow (RBF) on vascular function, endothelial biomarkers and repair capacity in healthy subjects and patients with hypertension. Main methods In seven healthy (CT; 32 ± 15 yr) and eight hypertensive (HT; 34 ± 23 yr) men, flow mediated-dilation (FMD) was assessed before and 10 min after a 30-min maneuver to increase brachial artery RBF in which a pneumatic cuff was inflated to 75 mm Hg on forearm. Blood samples were obtained at rest and during the last minute of the maneuver. Key findings Endothelial activation, apoptosis and endothelial progenitor cells (EPC) were measured by flow cytometry; nitrite was measured by ozone-chemiluminescence. No significant disparities were observed in FMD, endothelial activation and circulating EPC between groups at baseline (p > 0.05). However, HT presented higher resting endothelial apoptosis (p = 0.01 vs CT). Exacerbated RBF induced reductions in FMD (p = 0.02 vs baseline) and increases in endothelial activation in both groups (p = 0.049 vs baseline). Endothelial apoptosis increased only in HT (p = 0.02 vs baseline; p = 0.004 vs CT), whereas EPC (p = 0.02 vs baseline; p = 0.03 vs HT) and nitrite (p = 0.04 vs baseline; p = 0.004 vs HT) increased only in CT during the maneuver. Significance While findings indicate that increased RBF impairs endothelial function and triggers the EPC mobilization in healthy subjects, patients with hypertension presented greater apoptosis and impaired repair capacity in response to RBF.

Protein kinase C (PKC) pathway plays important roles in different phenomena in nervous system development. Our previous data demonstrated that phorbol 12-myristate 13-acetate (PMA) treatment, a PKC activator, for 48h decreases retinal cells proliferation by a mechanism mediated by muscarinic receptor activation, involving a decrease in M1 receptors levels. The aim of this work was to analyze how PMA interferes in the levels of cell cycle control proteins p53, p21 and cyclin D1 and also to investigate its influence on M3 receptor levels. Our results show that PMA (50ng/mL) produces a significant increase in p21 and p53 levels, decreases cyclin D1 levels, and also enhances M3 receptors levels in cell cultures. Evaluating the postnatal retinal tissue development until 30 days, we observed that tissue differentiation is accompanied by an increase in M3 and p21 levels. Based on our results we suggest that PMA treatment is promoting a change in muscarinic receptors expression mimicking the pattern observed during tissue differentiation, indicating that PMA is probably accelerating the cholinergic differentiation in rat retinal cell cultures.

Aims Increased matrix metalloproteinases activity and reduced nitric oxide (NO) bioavailability contributes to development of hypertension and this may be associated with a defective l -arginine-NO pathway. Exogenous l -arginine improves endothelial function to prevent the onset of cardiovascular disease, but the mechanism by which this is accomplished remains unclear. We determined the effects of exogenous l -arginine infusion on vascular biomarkers in patients with hypertension. Main methods Venous blood samples were obtained from seven patients with hypertension (45 ± 5 yrs., HT group) and eleven normotensive men (37 ± 3 yrs., CT group) before and during a 30-min intravenous l -arginine or saline infusion. Nitrite concentration was evaluated by ozone-chemiluminescence method; metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) activities were detected by zymography; tissue inhibitor of metalloproteinases-1 (TIMP-1) and 8-isoprostane concentrations were measured by enzyme-linked immunosorbent assay (ELISA); and thiobarbituric acid reactive substances (TBARS) were determined by colorimetric assay. Key findings At baseline, nitrite, TIMP-1, and MMP-2 activity were similar between the groups (P > 0.05), but MMP-9, TBARS and 8-isoprostane were higher in HT group (P ≤ 0.03). During l -arginine infusion, nitrite increased only in control group (P = 0.01), while MMP-2, MMP-9 activities, MMP-9/TIMP-1 ratio and 8-isoprostane decreased in HT group (P ≤ 0.02). There were no significant changes in vascular biomarkers between groups during the saline infusion (P > 0.05). Significance Exogenous l -arginine diminished metalloproteinase-2 and -9 activities and MMP-9/TIMP-1 ratio along with restoring the oxidative stress balance in patients with hypertension.

One of the central issues in neuroscience today is the study of the mechanisms of neuronal survival. Since the discovery of nerve growth factor (almost 60 years ago), many groups have clearly demonstrated the central role of neurotrophins on the regulation of neuronal cell survival during developmental stages as well as during adult life. However, neurotrophins are not alone in regulating neuronal survival, and many groups have demonstrated the effect of different cytokines on this phenomenon. In this brief review we will address the effect of interleukins (IL), particularly IL-2, IL-6, and IL-4, on the survival of neuronal cells.

Since 1973, multiple effects of basic fibroblast growth factor have been described in a large number of cells. These effects include proliferation, survival and differentiation. The aim of this work was to study the intracellular pathways involved in the basic fibroblast growth factor (FGF2) effect on rat retinal cells proliferation in vitro. Our data show that treatment with FGF2 increases proliferation in a concentration- and time-dependent manner. The effect of 25 ng/ml FGF2 was blocked by 10 microM genistein, a tyrosine kinase inhibitor and by 25 microM LY294002, a PI3 kinase inhibitor. The concomitant treatment with 0.3 microM chelerythrine chloride, a protein kinase C inhibitor, and 6.25 microM LY294002 also inhibited the effect of FGF2. Our results suggest that the proliferative effect of FGF2 on retinal cell cultures involves the activation of distinct kinases.