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).

[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.

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.

Effects of liposome-entrapped adenosine in the isolated rat aorta.

This study examined the effects of adenosine- and adenosine deaminase-loaded liposomes upon the contractile activity of the vascular smooth muscle, using the isolated, de-endothelised rat aorta ring as in vitro model. While control liposomes had no effect, intraliposomal adenosine (5 x 10(-3) M) induced contraction of the preparation. Intraliposomal adenosine deaminase induced partial relaxation of high K(+)-precontracted rings. The adenosine-induced contraction seems to involve Ca2+ influx through L-type channels as an essential component, but protein kinase C may also have a modulatory role.