Ghrelin and Ang 1-7 have cumulative vasodilatory effects on pulmonary vessels.

UNLABELLED: Ghrelin is an orexigenic hormone that has been shown to have vasodilator effects. Angiotensin 1-7 (Ang 1-7) is a bioactive component of the renin-angiotensin system and may play an important role in the regulation of cardiovascular homeostasis. AIM: The aim of this study was to investigate the interaction between ghrelin and a better known vasodilatator, Ang 1-7. MATERIAL AND METHOD: The dose-dependent relaxing effects of ghrelin were assessed on pulmonary artery rings of male Wistar rats with intact endothelium in the absence or the presence of Ang 1-7. Ang 1-7 was added in the organ bath with 5 minutes before N(G)-nitro L-arginine methyl ester (L-NAME, 1 micro/M) and indomethacin administration in the presence of cumulative doses of ghrelin. RESULTS: Our results showed that Ang 1-7 could improve and restore vasorelaxant effects of ghrelin on rat pulmonary rings with intact endothelium. CONCLUSION: Vasodilatatory actions of ghrelin are potentiated by Ang 1-7 and mediated by local synthesis of prostaglandins and nitric oxide.

[Involvement of angiotensin on adenosine-induced bronchial hyperreactivity]. / Implicarea angiotensinei in modularea hiperreactivitatii bronsice determinate de catre adenozina.

Adenosine is an endogenously purine nucleoside which plays a significant role in regulation of airways tone and reactivity by multiple and incompletely known mechanisms, including the release of endogenously active peptides from mast cells via activation of the A3 receptors. Our previous results suggested that releasing of enzymes from activated mast cells could activate the intrapulmonary renin angiotensin system (RAS). In this study, we investigated the involvement of angiotensin II (Ang II) in adenosine-induced bronchoconstriction in an experimental model of allergic asthma. On bronchial rings from ovalbumin (OVA) sensitized rats, after in vitro challenge, adenosine induced small contractile effects which became significant after indomethacin pre-treatment. On the other hand adenosine pre-treatment amplified bronchoconstriction induced by the allergen (OVA) challenge and reduced bronchial relaxation of acetylcholine pre-contracted bronchial rings by cumulative doses of terbutaline. All these effects are significantly lower on rats treated with losartan (a blocker of Ang II type 1 specific receptors, AT1) in the last two weeks of sensitization protocol (50 mg/kg/day). Our data confirmed that adenosine induced bronchial hyperreactivity could be partially a result of RAS activation in abnormal conditions as antigen sensitization and challenge.

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.

[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 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 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.