Endothelium-derived dopamine modulates EFS-induced contractions of human umbilical vessels.

Electrical field stimulation (EFS) induces contractions of both snake aorta and human umbilical cord vessels (HUCV) which were dependent on the presence of the endothelium. This study aimed to establish the nature of the mediator(s) responsible for EFS-induced contractions in HUCV. Rings with or without endothelium from human umbilical artery (HUA) or vein (HUV) were mounted in organ bath chambers containing oxygenated, heated Krebs-Henseleit's solution. Basal release of dopamine (DA), noradrenaline, and adrenaline was measured by LC-MS-MS. Cumulative concentration-response curves were performed with dopamine in the absence and in the presence of L-NAME or of dopamine antagonists. EFS studies were performed in the presence and absence of L-NAME, the α-adrenergic blockers prazosin and idazoxan, and the dopamine antagonists SCH-23390 and haloperidol. Tyrosine hydroxylase (TH) and dopa-decarboxylase (DDC) were studied by immunohistochemistry and fluorescence in situ hybridizations. Basal release of dopamine requires an intact endothelium in both HUA and HUV. TH and DDC are present only in the endothelium of both HUA and HUV as determined by immunohistochemistry. Dopamine induced contractions in HUA only in the presence of L-NAME. Dopamine-induced contractions in HUV were strongly potentiated by L-NAME. The EFS-induced contractions in both HUA and HUV were potentiated by L-NAME and inhibited by the D2-like receptor antagonist haloperidol. The α-adrenergic antagonists prazosin and idazoxan and the D1-like receptor antagonist SCH-23390 had no effect on the EFS-induced contractions of HUA and HUV. Endothelium-derived dopamine is a major modulator of HUCV reactivity in vitro.

Chronic ethanol consumption induces micturition dysfunction and alters the oxidative state of the urinary bladder.

Oxidative stress is pointed out as a major mechanism by which ethanol induces functional and structural changes in distinctive tissues. We evaluated whether ethanol consumption would increase oxidative stress and cause micturition dysfunction. Male C57BL/6J mice were treated with 20% ethanol (v/v) for 10 weeks. Our findings showed that chronic ethanol consumption reduced micturition spots and urinary volume in conscious mice, whereas in anaesthetized animals cystometric analysis revealed reduced basal pressure and increased capacity, threshold pressure, and maximum voiding. Treatment with ethanol reduced the contraction induced by carbachol in isolated bladders. Chronic ethanol consumption increased the levels of oxidant molecules and thiobarbituric acid reactive species in the mouse bladder. Upregulation of Nox2 was detected in the bladder of ethanol-treated mice. Increased activity of both superoxide dismutase and catalase were detected in the mouse bladder after treatment with ethanol. Conversely, decreased levels of reduced glutathione were detected in the bladder of ethanol-treated mice. The present study first demonstrated that chronic ethanol consumption induced micturition dysfunction and that this response was accompanied by increased levels of oxidant molecules in the mousebladder. These findings suggest that ethanol consumption is a risk factor for vesical dysfunction.

Effect of Polyphenols From Campomanesia adamantium on Platelet Aggregation and Inhibition of Cyclooxygenases: Molecular Docking and in Vitro Analysis.

Campomanesia adamantium is a medicinal plant of the Brazilian Cerrado. Different parts of its fruits are used in popular medicine to treat gastrointestinal disorders, rheumatism, urinary tract infections and inflammations. Despite its widespread use by the local population, the mechanisms involving platelet aggregation and the inhibition of cyclooxygenase by C. adamantium are unknown. This study evaluated the chemical composition, antioxidant activities and potential benefits of the C. adamantium peel extract (CAPE) and its components in the platelet aggregation induced by arachidonic acid in platelet-rich plasma. Aspects of the pharmacological mechanism were investigated as follows: platelet viability, calcium mobilization, levels of the cyclic nucleotides cAMP and cGMP, thromboxane B2 levels, and the inhibitory effects on COX-1 and COX-2 were studied in vitro and using molecular docking in the catalytic domain of these proteins. The major CAPE constituents standing out from the chemical analysis are the flavonoids, namely those of the flavones and chalcones class. The results showed that CAPE, quercetin and myricetin significantly decreased arachidonic acid-induced platelet aggregation; the assays showed that CAPE and quercetin decreased the mobilization of calcium and thromboxane B2 levels in platelets and increased cAMP and cGMP levels. Moreover, CAPE inhibited the activity of COX-1 and COX-2, highlighting that quercetin could potentially prevent the access of arachidonic acid more to the catalytic site of COX-1 than COX-2. These results highlight CAPE's potential as a promising therapeutic candidate for the prevention and treatment of diseases associated with platelet aggregation.