Apelin effects on lipopolysaccharide-increased pulmonary permeability in rats.

MATERIAL AND METHOD: Pretreatment with apelin-13 (AP-13, 2 mg/kg, i.p.), sodium butyrate (BUT, 200 mg/kg, s.c.) and N-acetyl-L-cysteine (NAC, 150 mg/kg, s.c.), all reduced the LPS-induced vascular leak measured as Evans blue extravasation, in rats lung tissue when compared to intranasal LPS (10 mg/100 mL) administered alone. RESULTS: Although there is a significant difference either between AP-13 and BUT on one hand, and NAC and BUT on the other hand pretreatments, there is no significant difference between AP-13 and NAC pretreatments. Firstly, apelin-13 pretreatment might justify its effects through the modulation of endothelial layer functions. We recently demonstrated that AP-13 could diminish the endothelial dysfunction of pulmonary vein from both ovalbumin sensitized rats and rats with pulmonary hypertension. Furthermore, pretreatment with AP-13 + BUT, AP-13+NAC as well as BUT+ NAC reduced the LPS-induced vascular leak when compared to LPS alone. The reduction effects of BUT and NAC association were higher than those of either BUT or NAC alone. These synergistic effects might be associated to different and additive mechanisms of action of BUT and NAC. Thus, BUT might be primarily effective on macrophage migration and secondarily on activation and cytokine secretion by macrophages and NAC might be primarily effective on macrophages activation. Furthermore, since there are no significant effects between AP-13, NAC and AP-13+NAC we can conclude that AP-13 and NAC effects might be mediated through the same mechanisms (with the possible involvement of nuclear transcription factor NF-kB).

Adenosine involvement on bronchial reactivity modulation by diesel exhaust.

UNLABELLED: In recent decades, epidemiologic investigations have suggested a strong relationship between air pollution and an increase in the prevalence of allergic rhinitis and asthma. AIM: To investigate the possible involvement of adenosine (AD) in bronchomotor effects of diesel exhaust (DE). MATERIAL AND METHOD: Isolated bronchi from ovalbumin (OVA) sensitized rats were challenged in presence or absence of diesel exhaust extract (DEE). AD was delivered on organ bath before or after DEE, at concentrations did not produce significantly contractile effects. RESULTS: AD (0.1 microM) pre-treatment increased bronchomotor effects of DEE: amplified the bronchoconstrictor effects of OVA with more than 35% and decreased Emax of terbutaline induced bronchorelaxation of acetylcholine (Ach) preconstricted bronchial rings (up to 20%), but did not significantly modify ACh-induced contractions. OVA-induced contractions, ACh-induced contractions and terbutaline-induced relaxations have not been significantly modified as compare with DEE alone. On the other hand, DEE amplified AD (cumulative doses) contractile effects. CONCLUSION: These results confirmed our initial hypothesis that AD could partial mediate or at least, modulate DEE effects on airway reactivity.

[Estimation of uncertainty of measurement in clinical biochemistry]. / Incertitudinea de masurare. Posibilitati de estimare in masuratorile cantitative din laboratoarele de analize medicale.

The uncertainty of measurement (UM) or measurement uncertainty is known as the parameter associated with the result of a measurement. Repeated measurements usually reveal slightly different results for the same analyte, sometimes a little higher, sometimes a little lower, because the results of a measurement are depending not only by the analyte itself, but also, by a number of error factors that could give doubts about the estimate. The uncertainty of the measurement represent the quantitative, mathematically expression of this doubt. UM is a range of measured values which is probably to enclose the true value of the measured. Calculation of UM for all types of laboratories is regularized by the ISO Guide to the Expression of Uncertainty in Measurement (abbreviated GUM) and the SR ENV 13005 : 2003 (both recognized by European Accreditation). Even if the GUM rules about UM estimation are very strictly, the offering of the result together with UM will increase the confidence of customers (patients or physicians). In this study the authors are presenting the possibilities of UM assessing in labs from our country by using the data obtained in the procedures of methods validation, during the internal and external quality control.

Adipokines involvement in lung function.

The last two decades brings many data about white adipose tissue capacity to secrete hormones, named adipokines, which could mediate the relationship between obesity and lung diseases. In this paper we presented some data about adipokines involvement on pulmonary function, with special emphasis on leptin, adiponectin, tumor necrosis factor alpha, vascular endothelial growth factor, resistin, hepatocyte growth factor, interleukin-6, angiotensinogen and apelin.

[New insight into nitric oxide involvement in regulation of airways smooth muscle tone]. / New insight into nitric oxide involvement in regulation of airways smooth muscle tone.

UNLABELLED: All three isoforms of NO synthases (NOS) were localised in the lung and are involved in regulation of airways and pulmonary vessels smooth muscle tone and inflammatory response. The participation of nitric oxide in the regulation of airways smooth muscle has not been understood yet. MATERIAL AND METHOD: We studied age-related variation of NO secretion on three lots of bronchi rats: young (4-6 weeks), adults (2-3 months), old (12-14 months). The implied of NO synthesis on airways smooth muscle tone was indirectly investigated by blocking NOS with N(omega)-nitro-L-arginine methyl ester (L-NAME). RESULTS: Pre-treatment of isolated bronchi rings with 0.1 mM L-NAME amplified both tonic contractions induced by cumulative doses of acetylcholine (0.1 nM - 1mM) and various doses of angiotensin II (10 nM - 10 eM). L-NAME actions were lower on old than young rats: at least two times for ACh and three times for Ang II. These results suggest that NO actions decrease with age. Decrease of NO activity on airways was described in pathological states like asthma. CONCLUSIONS: Decrease of NO activity would generate increase of airway smooth muscle tone and would explain partially aging changes on airway reactivity.

[Interactions between angiotensin II and theophylline on isolated rat bronchi]. / Interactiunea angiotensina II--teofilina pe inele de bronhie de sobolan.

UNLABELLED: For more than half of century physicians are using theophylline for the treatment of obstructive pulmonary diseases. Because our previously results suggested the amplification of intrapulmonary renin angiotensin system (RAS) on ovalbumin (OVA) induced airway hyperresponsiveness we studied the interaction between theophylline and angiotensin II (Ang II) on normal versus sensitized rats. MATERIALS AND METHODS: we used main left bronchial rings mounted in wire myograph to assess the effects of Ang II and theophylline on airway smooth muscle. RESULTS: On both normal and OVA sensitized rats theophylline did not significantly modify either Ang II contractile effects or Ang II amplification of acetylcholine (ACh)-induced bronchoconstriction. On the other hand, on sensitized rat after antigen challenge, theophylline pretreatment reduced Ang II inhibition of terbutaline--induced relaxation of bronchial rings precontracted with ACh, increasing both EC50 and E(max) of terbutaline effects with 22.04 +/- 3.48% and 19.48 +/- 1.67%, respectively. CONCLUSION: These findings suggested that, in addition to bronchodilatory and antiinflammatory actions, theophylline could block some effects of intrapulmonary RAS activated in pathologically states as antigen sensitization and challenge.

Contractile effects of angiotensinogen and its multiple metabolization pathways on vessel walls.

The contractile effects of angiotensinogen (Aogen) and its metabolization pathways were studied on rat renal vein (RRV), rat pulmonary artery (RPA) and human umbilical vein (HUV) rings. Experiments were made in the presence or in the absence of pepstatin A (a renin inhibitor, 10 microM), captopril (an ACE inhibitor, 10 microM), chymostatin (a chymase inhibitor, 10 microM), amastatin (an aminopeptidase-A and -M inhibitor) or losartan (a specific AT1 blocker, 10 microM). On all rings, Aogen-induced contractions were reduced by pepstatin A or captopril, amplified by amastatin and blocked by losartan. Chymostatin had a stronger inhibitory effect than captopril on HUV and simultaneous administering of chymostatin and captopril prevented Aogen contractile effects on HUV. It is suggested that all studied vessels possess a local renin-angiotensin system and possibility of angiotensin II production within the vessel walls using various and species-dependent enzymatic pathways.

Interactions between angiotensin II and phenylephrine on isolated rat renal arteries and veins.

It is know that not only decreased blood flow to the kidney but also obstruction of renal outflow may, in some instances, be a cause of hypertension. In this view were compared angiotensin (Ang) II responses and investigated interactions between Ang II and phenylephrine (Phe) on renal vessels. Studies were performed on renal artery and vein rings without endothelium obtained from young (4 months) and old (12 month of age) male Wistar rats. As compared with control contractions (40 microM KC1) there are no differences between renal artery and veins on Phe- or Ang II-induced contractions. Phe -induced contractions after 1 microM Ang II pretreatment were higher on renal veins than arteries. Ang II administered after 1 microM Phe could additional increase Phe-induced contractions only on renal veins. On the other hand, these differences between renal arteries and veins responses were significantly higher on rings obtained from old as compared those from young rats. These age-dependent differences between renal artery and vein reactivity can be a possible cause of input-output renal blood flow unbalance and might become important in some pathological states which associate sympathetic activation with hyperreninemia.

Interactions between angiotensin I and acetylcholine on rat left main bronchial rings.

Angiotensin (Ang) II is known to amplified bronchoconstriction induced by acetylcholine (ACh). On the other hand all the components of renin angiotensin system were located on lungs. Contractile effects of Ang I (the precursor of Ang II) and interactions between Ang I and ACh on rat bronchial rings were characterize using angiotensin II type 1 (AT1) receptor antagonist (losartan), angiotensin converting enzyme (ACE) inhibitors (captopril and teprotide) and chymase inhibitor (chymostatin). We found that Ang I has contractile effects and amplified ACh-induced contractions. Blocking of AT1 receptors with 10 mM losartan significantly reduced 10 mM Ang I contractile effects (12.79 +/- 9.59% from 167.62 +/- 8.92%; p<0.05). Pre-treatment with 1 mM teprotide reduced 10 mM Ang I-induced contractions (35.68 +/- 7.83%; p>0.05). Captopril and teprotide only reduced Ang I actions. This suggested that both types of Ang I effects were mediated by AT1 receptors, but possibly conversion of Ang I into Ang II were not significantly dependent by ACE or chymase.

Interactions between extracellular and intracellular administered angiotensin II in isolated rat portal vein rings.

It is already demonstrated that intracellular angiotensin II (Ang II) stimulates smooth muscle contraction and cell growth. We studied the contractile effects of Ang II intracellular delivered by the means of liposomes (LAngII) and also the interactions between intracellular and extracellular administered Ang II on the rat portal vein rings without endothelium. The results were expressed as the percentages of the control contraction (K+ 40 mM; mean +/- S.E.M). LAngII induced contractions were of 120.46 +/- 8.06%. On the other hand, 0.1 microM Ang II produced contractions of 121.43 +/- 6.83%. Both Ang II and losartan, administered either extracellular in the organ bath or intracellular by the means of liposomes, inhibited the contractions induced by intracellular Ang II. The inhibitory effects of losartan on LAngII-induced contractions were dose-dependent. Thus, 10 microM losartan strongly blocked (10.01 +/- 1.41%) and 1 microM losartan partially blocked (39.73 +/- 5.35%) the LAngII-induced effects. LLOS significantly inhibited the LAngII contractile effects (38.51 +/- 8.92%). Our results revealed that LAngII partially inhibited the contractions induced by extracellular administered Ang II (42.42 +/- 3.29%). On the other hand, 0.1 microM Ang II also inhibited the contractile effects induced by LAngII (67.42 +/- 0.76%), although a little bit less. So, contractions induced by Ang II administered intracellular are mainly mediated by intracellular Ang II receptors sensitive to losartan. At the same time, the participation of cell membrane angiotensin receptors to intracellular Ang II effects cannot be excluded.

[Interactions between angiotensin-(1-7)and angiotensin II in isolated rat portal vein]. / Interactiuni ale Angiotensinei-(1-7) cu Angiotensina II la nivelul venei porte izolate de sobolan.

Our preliminary data show for the first time the interaction between angiotensin-(1-7) (Ang-(1-7)) and angiotensin II (Ang II, 10 nM) in isolated rat portal vein. Very low concentrations (10 nM) of Ang-(1-7) have marked functional antagonizing effects on Ang II-induced contractions. High concentrations of Ang-(1-7) (1-10 mM) do not affect the effects of Ang II. The effects of low concentration Ang-(1-7) might be associated to the interaction with Ang-(1-7) specific receptors and the own contractile effects (approximatively 28%) at high concentrations might be assign to the interaction with angiotensin specific receptors AT1. But, the lack of effects of Ang-(1-7) high concentrations on Ang II-induced contractions hardly might be associated to the interaction with AT1 receptors. Although losartan was entirely blocking the Ang-(1-7) effects, there is in the literature a series of data showing that Ang-(1-7) specific receptors (or a subtype of Ang-(1-7) receptors) might be sensible (with possible high affinity) to losartan. Additional experiments are thus necessary to further clarify these interactions.

[Alternative pathways for the activation of the renin-angiotensin system]. / Cai alternative de activare ale sistemului renina-angiotensina.

The knowledge of the structure and function of the components of the renin-angiotensin system (RAS) is rapidly increasing. The classic pathway of angiotensin (Ang) II generation includes a reaction catalyzed by angiotensin-converting enzyme (ACE). We actually discuss the alternative pathways for the generation of Ang-II and other angiotensin peptides (Ang III, Ang IV, Ang (1-9), Ang (1-7), des-Asp-Ang I) and the responsible enzymes (tonins, cathepsins, chymases, aminopeptidases, dipeptidyl aminopeptidases, neutral endopeptidases, carboxypeptidases, ACE2 etc.). The development of novel enzyme inhibitors (e.g., nafamostat, sampatrilat) for more efficacious suppression of RAS activity is also considered.