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- ItemSomente MetadadadosDifferent mechanism of LPS-induced vasodilation in resistance and conductance arteries from SHR and normotensive rats(Nature Publishing Group, 2002-09-01) Farias, Nelson C.; Borelli-Montigny, Gisele L.; Fauaz, Grasiele; Feres, Teresa; Borges, Antonio Carlos R [UNIFESP]; Paiva, Therezinha B. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)1 the direct and endothelium-dependent effects of lipopolysaccharide (LPS) were investigated on resistance and conductance arteries from normotensive Wistar (NWR) and spontaneously hypertensive (SHR) rats.2 in both NWR and SHR, LPS induced dose-dependent relaxations of the mesenteric vascular bed, which were inhibited by L-NNA in SHR but not in NWR. Iberiotoxin (IBTX) inhibited the responses to LPS in both groups, indicating the participation of high conductance Ca2+-dependent K+ channels.3 in mesenteric artery rings, the resting membrane potentials and the hyperpolarizing responses of NWR to LPS did not differ in endothelized and denuded preparations but L-NNA inhibited the responses only in endothelized rings. These responses were reduced by bosentan, suggesting that endothelin release may mask a possible hyperpolarizing response to LPS. the hyperpolarizing responses to LPS were blocked by IBTX in both endothelized and de-endothelized NWR rings. in the SHR only intact rings showed hyperpolarization to LPS, which was inhibited by IBTX and by L-NNA.4 in SHR aortic endothelized or denuded rings, LPS induced hyperpolarizing responses which, in endothelized rings, were partially blocked by L-NNA, by IBTX or by glibenclamide, but totally abolished by IBTX plus glibenclamide. No response to LPS was observed in NWR aortic rings.5 Our results indicate that LPS activates large conductance Ca2+-sensitive K+ channels located in the smooth muscle cell membrane both directly and indirectly, through NO release from the endothelium in NWR, whereas NO is the major mediator of the LPS responses in SHR resistance vessels.
- ItemSomente MetadadadosEffect of treatment with cholecalciferol on the membrane potential and contractility of aortae from spontaneously hypertensive rats(Stockton Press, 1996-07-01) Silva, Eneida de Gusmao [UNIFESP]; Fredianineto, E.; Ferreira, A. T.; Paiva, Antonio Cechelli de Mattos[UNIFESP]; Paiva, Therezinha Bandiera [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)1 The diet of spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NWR) was supplemented with 12.5 mu g cholecalciferol per 100 g body weight daily, by gavage, for 4 weeks.2 The amplitude of the contractile responses of aortic rings from SHR to potassium and adrenaline, which was smaller than in NWR aortae, was increased after treatment with cholecalciferol. No further changes were observed in the responses of NWR and SHR aortae in the presence of 100 nM apamin.3 The membrane potentials of aortae from SHR, which were higher than those of aortae from NWR, decreased after treatment with cholecalciferol. Further depolarization was observed in aortic rings from NWR, but not in aortic rings from SHR, after their preincubation with 100 nM apamin.4 It is concluded that cholecalciferol normalizes the membrane potential and contractility of aortae from SHR, probably through an effect on lipid composition and structure of the plasma membrane.
- ItemSomente MetadadadosEffects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade(Stockton Press, 1999-08-01) Pupo, André S.; Cavenaghi, Daniela LC; Campos, Marcelo; Morais, Paola D.; Jurkiewicz, Neide Hyppolito [UNIFESP]; Jurkiewicz, Aron [UNIFESP]; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)1 the actions of the alpha(1)-adrenoceptor antagonist indoramin have been examined against the contractions induced by noradrenaline in the rat vas deferens and aorta taking into account a putative neuronal uptake blocking activity of this antagonist which could. result in self-cancelling actions.2 Indoramin behaved as a simple competitive antagonist of the contractions induced by noradrenaline in the vas deferens and aorta yielding pA(2) values of 7.38 +/- 0.05 (slope = 0.98 +/- 0.03) and 6.78 +/- 0.14 (slope = 1.08 +/- 0.06), respectively.3 When the experiments were repeated in the presence of cocaine (6 mu M) the potency (pA(2)) of indoramin in antagonizing the contractions of the vas deferens to noradrenaline was increased to 8.72 +/- 0.07 (slope = 1.10 +/- 0.05) while its potency remained unchanged in the aorta (pA(2) = 6.69 +/- 0.12; slope = 1.04 +/- 0.05).4 in denervated vas deferens, indoramin antagonized the contractions to noradrenaline with a potency similar to that found in the presence of cocaine (8.79 +/- 0.07; slope = 1.09 +/- 0.06).5 It is suggested that indoramin blocks alpha(1)-adrenoceptors and neuronal uptake in rat vas deferens resulting in Schild plots with slopes not different from unity even in the absence of selective inhibition of neuronal uptake. As a major consequence of this double mechanism of action, the pA(2) values for this antagonist are underestimated when calculated in situations where the neuronal uptake is active, yielding spurious pK(B) values.
- ItemSomente MetadadadosHeparin Induces Rat Aorta Relaxation via Integrin-Dependent Activation of Muscarinic M-3 Receptors(Lippincott Williams & Wilkins, 2010-10-01) Paredes-Gamero, Edgar Julian [UNIFESP]; Medeiros, Valquiria Pereira de [UNIFESP]; Farias, Eduardo Henrique Cunha de [UNIFESP]; Justo, Giselle Zenker [UNIFESP]; Trindade, Edvaldo da Silva [UNIFESP]; Andrade-Lopes, Ana L.; Godinho, Rosely Oliveira [UNIFESP]; Miranda, Antonio [UNIFESP]; Ferreira, Alice Teixeira [UNIFESP]; Tersariol, Ivarne Luis dos Santos [UNIFESP]; Nader, Helena Bonciani [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Fed ParanaPrevious reports have shown that heparin may promote human hypotension and vascular relaxation by elevation of NO levels through unclear mechanisms. We hypothesized that endothelial muscarinic M-3 receptor activation mediates the heparin-induced vasodilation of rat aortic rings. the experiments were carried out using unfractionated heparin extracted from bovine intestinal mucosa, which elicited an endothelium and NO-dependent relaxation of aortic segments with maximal potency and efficacy (EC50: 100 +/- 10 mu mol/L; E-max: 41 +/- 3%). Atropine and 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide inhibitors reduced the heparin-dependent relaxation, indicating that M-3 muscarinic receptor is involved in this phenomenon. However, no direct binding of heparin to muscarinic receptors was observed. More importantly, studies performed using the arginine-glycine-aspartic acid peptide and 1-(1,1-dimethylethyl)-3-(1-naphthalenyl)-1H-pyrazolo[3,4-day]pyrimidin-4-amine, an Src family inhibitor, reduced by 51% and 73% the heparin-dependent relaxation, respectively, suggesting the coupling of heparin and M-3 receptor through extracellular matrix molecules and integrin. Furthermore, unfractionated heparin induced activation of focal adhesion protein kinase, Src, and paxillin. Finally, fluorescence resonance energy transfer approach confirmed the interaction of the M-3 receptor to integrin. Taken together, these data demonstrate the participation of M-3 receptor and integrin in heparin-dependent relaxation of vascular smooth muscle. These results provide new insights into the molecular mechanism and potential pharmacological action of heparin in vascular physiology. (Hypertension. 2010;56:713-721.)
- ItemSomente MetadadadosLys-[Leu(8),des-Arg(9)]-bradykinin blocks lipopolysaccharide-induced SHR aorta hyperpolarization by inhibition of Ca++- and ATP-dependent K+ channels(Elsevier B.V., 2004-09-13) Farias, N. C.; Feres, T.; Paiva, ACM; Paiva, T. B.; Universidade Federal de São Paulo (UNIFESP)The mediators involved in the hyperpolarizing effects of lipopolysaccharide and of the bradykinin B, receptor agonist des-Arg(9)-bradykinin on the rat aorta were investigated by comparing the responses of aortic rings of spontaneously hypertensive and normotensive Wistar rats. Endothelized rings from hypertensive rats were hyperpolarized by des-Arg(9)-bradykinin and lipopolysaccharide, whereas deendothelized rings responded to lipopolysaccharide but not to des-Arg(9)-bradykinin. in endothelized preparations, the responses to des-Arg(9)-bradykinin were inhibited by N-nitro-L-arginine and iberiotoxin. De-endothelized ring responses to lipopolysaccharide were inhibited by iberiotoxin, glibenclamide and B, antagonist Lys-[Leu(8),des-Arg(9)]-bradykinin. This antagonist also inhibited hyperpolarization by des-Arg(9)-bradykinin and by the a(2)-adrenoceptor agonist, brimonidine. Our results indicate that Ca2+-sensitive K+ channels are the final mediators of the responses to des-Arg(9)-bradykinin, whereas both Ca2+- and ATP-sensitive K+ channels mediate the responses to lipopolysaccharide. the inhibitory effects of Lys-[Leu(8),des-Arg(9)]-bradykinin is due to a direct action on Ca2+- and ATP-sensitive potassium channels. (C) 2004 Elsevier B.V All rights reserved.
- ItemSomente MetadadadosPrediction of fetal anemia by Doppler of the middle cerebral artery and descending thoracic aorta(Springer, 2008-07-01) Pares, David [UNIFESP]; Chinen, Paulo A. [UNIFESP]; Camano, Luiz [UNIFESP]; Moron, Antonio F. [UNIFESP]; Torloni, Maria R. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Background Despite significant advances, perinatal hemolytic disease has not been eradicated and is still associated with significant morbidity and mortality, especially in developing countries. An accurate method for antenatal diagnosis and quantification of fetal anemia is a crucial step prior to the performance of invasive procedures, which are not risk-free. the middle cerebral artery peak systolic velocity (MCA-PSV) is currently the most popular non-invasive diagnostic method used to quantify fetal anemia and determine the exact timing for transfusion the combined use of MCA-PSV and descending thoracic aorta mean velocity (DTA-MV) has not been previously evaluated. Since this strategy has the potential to decrease false positive results it could reduce unnecessary cordocenteses, therefore minimizing fetal risks. This study aimed to evaluate the accuracy of MCA-PSV associated with DTA-MV in the prediction of fetal anemia.Method Retrospective analysis of 90 cordocenteses performed on alloimmunized pregnancies in a single hospital MCA-PSV and DTA-MV were performed immediately before cordocentesis. the Dopplervelocimetry findings were compared with fetal hemoglobin concentration. Sensitivity, specificity, positive and negative predictive values and accuracy of MCA-PSV and DTA-MV in the prediction of moderate/severe fetal anemia were calculated.Results the individual sensitivity of MCA-PSV and DTA-MV was 100 and 95.7%, specificity was 65 and 100% and accuracy was 92.2 and 96.7%, respectively. the combination of both vessels produced a higher overall accuracy (98.6%).Conclusion MCA-PSV is more sensitive and DTA-MV is more specific in the detection of fetal anemia. the highest diagnostic accuracy was obtained by the association of both Doppler evaluations.