1. The aim of the present study was to examine the effect of chronic administration of aspirin on metabolic and cardiovascular parameters in fructose-fed rats (FFR), an experimental model of metabolic syndrome. 2. Chronic treatment of FFR with aspirin (10 mg/kg per day for 6 weeks) partially reversed the increment in systolic blood pressure. In addition, chronic aspirin treatment normalized relative heart weight and vascular remodelling of renal and carotid arteries, measured as lumen diameter: medial thickness ratio. 3. Furthermore, chronic aspirin administration completely reversed glucose intolerance and decreased the oxidative status that characterizes the FFR model, as indicated by decreased plasma levels of thiobarbituric acid-reactive substances and aortic NAD(P)H oxidase activity. 4. Prevention of oxidative stress and vascular remodelling in FFR may contribute to the protective actions attributed to aspirin in the treatment of metabolic syndrome.

1 Administration of bradykinin caused dose-dependent vasoconstriction in rat isolated perfused mesenteric arteries precontracted with noradrenaline.2 The vasoconstrictor response was not mediated by BK1-bradykinin receptors.3 Inhibition of cyclo-oxygenase with indomethacin, aspirin or meclofenamate abolished the vasoconstrictor effect of bradykinin, showing that a member of the arachidonic acid cascade may be involved. 4 Inhibitors of thromboxane synthesis (imidazole and UK 38485) did not affect or only reduced the bradykinin-induced vasoconstriction. 5 The endoperoxide H2/thromboxane A2 receptor antagonist SQ 29548 significantly reduced the vasoconstrictor effect of bradykinin, but did not affect the vasoconstrictor response to noradrenaline, adrenaline, vasopressin, 5-hydroxytryptamine or prostaglandins. 6 The eicosanoid(s) that mediate bradykinin-induced vasoconstriction appear to be synthesized outside the arterial endothelium. 7 The data suggest that the vasoconstrictor effect of bradykinin in the rat isolated mesenteric artery is mediated by vasoconstrictor arachidonic acid metabolites including the cyclic endoperoxides and/or the thromboxanes.

We assessed immunoreactivity (IR) in the cerebral cortex (CC), hippocampus (Hipp), and striatum (ST) of a growth-associated protein, GAP-43, and of proteins of the synaptic vesicle fusion complex: VAMP-2, Syntaxin-1, and SNAP-25 (SNARE proteins) throughout postnatal development of rats after submitting the animals to acute global postnatal hypoxia (6.5% O(2), 70 min) at postnatal day 4 (PND4). In the CC only the IR of the SNARE protein SNAP-25 increased significantly with age. The hypoxic animals showed the same pattern of IR for SNAP-25, although with lower levels at PND11, and also a significant increase of VAMP-2. SNAP-25 (control): PND11 P < 0.001 vs. PND18, 25, and 40, SNAP-25 (hypoxic): P < 0.001 vs. PND18, 25, and 40; VAMP-2 (hypoxic): P < 0.05 PND11 vs. PND18, and P < 0.01 vs. PND25 and PND40; one-way ANOVA and Bonferroni post-test. In the Hipp, SNAP-25 and syntaxin-1 increased significantly with age, reaching a plateau at PND25 through PND40 in control animals (one-way ANOVA: syntaxin-1: P = 0.043; Bonferroni: NS; SNAP-25: P = 0.013; Bonferroni: P < 0.01 PND11 vs. PND40). Hypoxic rats showed higher levels of significance in the one-way ANOVA than controls (syntaxin-1: P = 0.009; Bonferroni: P < 0.05 PND11 vs. PND25 and P < 0.001 PND11 vs. PND40). In the ST, GAP-43 differed significantly among hypoxic and control animals and the two-way ANOVA revealed significant differences with age (F = 3.23; P = 0.037) and treatment (F = 4.84; P = 0.036). VAMP-2 expression also reached statistical significance when comparing control and treated animals (F = 6.25, P = 0.018) without changes regarding to age. Elevated plus maze test performed at PND40 indicated a lower level of anxiety in the hypoxic animals. At adulthood (12 weeks) learning, memory and locomotor abilities were identical in both groups of animals. With these results, we demonstrate that proteins of the presynaptic structures of the ST are sensitive to acute disruption of homeostatic conditions, such as a temporary decrease of the O(2) concentration. Modifications in the activity of these proteins could contribute to the long term altered responses to stress due to acute hypoxic insult in the neonatal period.

We performed this study to examine the presence of a kallikrein-kinin system in rat fetal and maternal tissues. Uteri and placenta from Wistar pregnant and nonpregnant rats were perfused to eliminate blood, and fetal membranes were washed several times with saline. Amniotic fluids were obtained without blood contamination by amniocentesis from eight rats. The different samples were homogenized and centrifuged (2000g during 20 minutes), and the supernatant was incubated with dog kininogen and 0.1 mol/L Tris-HCl buffer (pH 8.5) in the presence of peptidase inhibitors. Kinins released were measured by radioimmunoassay. Kininogenase activity was found in rat uteri, placental vessels, amniotic fluids, and fetal membranes. The enzymes were present in active but mostly in inactive forms. The kallikrein-like enzymes found in the different preparations and rat urinary kallikrein used as control had similar molecular weights, immunologic characteristics, and inhibition profiles with protease inhibitors. We conclude that kallikrein-like enzymes are present in rat organs of reproduction. These data suggest that kinins released locally may act as paracrine hormones in the regulation of blood pressure during pregnancy. changes that enable the gravida to accommodate the growing products of conception. These changes -quite profound in the cardiovascular system, kidney, and uterus-have been characterized extensively but never understood completely. Despite increases in plasma volume and cardiac output, blood pressure actually declines.1 This reduction occurs because peripheral vascular resistance in pregnancy decreases significantly from normal nonpregnant levels. 2The renin-angiotensin-aldosterone system is activated markedly during pregnancy.3 Decreased blood pressure in the face of elevated plasma levels of angiotensin suggests that pregnant women are resistant to the pressor effect of angiotensin. Precisely why pregnancy reduces peripheral vascular resistance is unknown. Recently, it has been proposed that the reduced peripheral vascular resistance is due to an increased production of vasodilator substances. 4 Kinins are potent vasodilator peptides released from kininogen by kininogenases. There is now clear evidence that part of the hemodynamic effect of kinins are mediated by prostaglandins and endothelium-derived relaxing factors. Kallikrein has been implicated in the regulation of uteroplacental blood flow 57 ; however, whether or not kallikrein can be found within these tissues is not known. Although kinin-forming activity has been reported in human organs of reproduction, 8 further characterization is needed because proteases other than kallikrein can also release kinins. In this study we examined the presence and biochemical characteristics of kallikrein-like enzymes in the uteroplacental-fetal complex. MethodsAdult female Wistar rats between 14 and 15 days' gestation (term rat pregnancy, 22 days) weighing 200 to 250 g were anesthetized with sodium pentobarbital (50 mg/kg IP). The animals were treated in acco...