Endothelin-induced vascular and bronchial effects in pig airways: role in acute allergic responses

2002 ◽  
Vol 93 (5) ◽  
pp. 1608-1615 ◽  
Author(s):  
H. Sylvin ◽  
E. Weitzberg ◽  
K. Alving
Keyword(s):  
Vascular Tone ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
No Synthase ◽  
Vascular Conductance ◽  
Intravenous Injections ◽  
Selective Agonist ◽  
Acute Airway Obstruction ◽  
Airway Mechanics ◽  
Synthase Inhibitor

The effects of endothelin (ET) agonists on airway mechanics and bronchial blood flow were studied as well as the effects of mixed ET-receptor antagonist bosentan on allergen-induced airway reactions in the pig. ET agonists [ET-1, ET-3, and the ETB receptor-selective agonist Sarafotoxin 6c (Sf6c)] were given as intravenous injections (0.4–200 pmol/kg) to eight anesthetized pigs. Bosentan (10 mg/kg iv) was then administered, and the injections were repeated. Only Sf6c caused a significant increase in airway resistance, and this response was blocked by bosentan. Sf6c and ET-1 (200 and 400 pmol/kg, respectively) were also given as aerosols to five pigs. Sf6c, but not ET-1, caused bronchoconstriction via this route. All agonists (intravenous) caused increases in bronchial vascular conductance, an effect that was blocked by an NO-synthase inhibitor ( N G-nitro-l-arginine) but unaffected by a cyxlooxygenase inhibitor (diclofenac). Fourteen pigs were sensitized with ascaris suum antigen. Under anesthesia, eight pigs were pretreated with bosentan, and six pigs were controls. They were all challenged with allergen aerosol resulting in acute bronchoconstriction and elevation of ET-1 in bronchoalveolar lavage fluid. Bosentan did not affect the maximal acute airway obstruction but markedly increased baseline bronchial vascular conductance, suggesting a basal vascular tone regulated by ETs. In conclusion, ETs induce bronchoconstriction primarily via the ETB receptor in the pig. However, ETs are probably not involved in the allergen-induced acute bronchoconstriction in this model.

Leukotriene B4 induces airway hyperresponsiveness in dogs

1985 ◽  
Vol 59 (6) ◽  
pp. 1941-1946 ◽  
Author(s):  
P. M. O'Byrne ◽  
G. D. Leikauf ◽  
H. Aizawa ◽  
R. A. Bethel ◽  
I. F. Ueki ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Leukotriene B4 ◽  
Airway Responsiveness ◽  
Thromboxane B2 ◽  
Neutrophil Chemotaxis ◽  
Pulmonary Resistance ◽  
Thromboxane Synthase Inhibitor ◽  
Synthase Inhibitor ◽  
Cellular Components

We studied the effect of leukotriene B4 aerosols on airway responsiveness to inhaled acetylcholine aerosols and on the cellular components and cyclooxygenase metabolites in bronchoalveolar lavage fluid in dogs. Inhalation of leukotriene B4 aerosols had no effect on resting total pulmonary resistance but increased airway responsiveness, an effect that was maximum in 3 h and that returned to control levels within 1 wk. Three hours after leukotriene B4, the number of neutrophils and the concentration of thromboxane B2 recovered in lavage fluid increased markedly. Pretreatment with the thromboxane synthase inhibitor OKY-046 prevented the increases in airway responsiveness and in thromboxane B2 but did not alter neutrophil chemotaxis. Thus we speculate that leukotriene B4 causes neutrophil chemotaxis and release of thromboxane B2, which increases airway responsiveness.

Bicarbonate-dependent superoxide release and pulmonary artery tone

2003 ◽  
Vol 285 (6) ◽  
pp. H2327-H2335 ◽  
Author(s):  
Eva Nozik-Grayck ◽  
Yuh-Chin T. Huang ◽  
Martha Sue Carraway ◽  
Claude A. Piantadosi
Keyword(s):  
Methyl Ester ◽  
Pulmonary Artery ◽  
Vascular Tone ◽  
Plasma Membranes ◽  
Vascular Reactivity ◽  
No Synthase ◽  
Pulmonary Vasoconstriction ◽  
Anion Exchange Protein ◽  
Hypoxic Vasoconstriction ◽  
Synthase Inhibitor

Pulmonary vasoconstriction is influenced by inactivation of nitric oxide (NO) with extracellular superoxide ([Formula: see text]). Because the short-lived [Formula: see text] anion cannot diffuse across plasma membranes, its release from vascular cells requires specialized mechanisms that have not been well delineated in the pulmonary circulation. We have shown that the bicarbonate [Formula: see text] anion exchange protein (AE2) expressed in the lung also exchanges [Formula: see text] for [Formula: see text]. Thus we determined whether [Formula: see text] release involved in pulmonary vascular tone depends on extracellular [Formula: see text]. We assessed endothelium-dependent vascular reactivity and [Formula: see text] release in the presence or absence of [Formula: see text] in pulmonary artery (PA) rings isolated from normal rats and those exposed to hypoxia for 3 days. Lack of extracellular [Formula: see text] in normal PA rings significantly attenuated endothelial [Formula: see text] release, opposed hypoxic vasoconstriction, and enhanced acetylcholine-mediated vasodilation. Release of [Formula: see text] was also inhibited by an AE2 inhibitor (SITS) and abolished in normoxia by an NO synthase inhibitor ( NG-nitro-l-arginine methyl ester). In contrast, hypoxia increased PA AE2 protein expression and [Formula: see text] release; the latter was not affected by NG-nitro-l-arginine methyl ester or other inhibitors of enzymatic [Formula: see text] generation. Enhanced [Formula: see text] release by uncoupling NO synthase with geldanamycin was attenuated by hypoxia or by [Formula: see text] elimination. These results indicate that [Formula: see text] produced by endothelial NOS in normoxia and unidentified sources in hypoxia regulate pulmonary vascular tone via AE2.

Role of nitroxidergic nerve in dog retinal arterioles in vivo and arteries in vitro

1994 ◽  
Vol 266 (5) ◽  
pp. H1985-H1992 ◽  
Author(s):  
N. Toda ◽  
Y. Kitamura ◽  
T. Okamura
Keyword(s):  
Muscle Tone ◽  
No Synthase ◽  
Intravenous Injections ◽  
Retinal Arterioles ◽  
Anesthetized Dogs ◽  
Retinal Artery ◽  
Synthase Inhibitor

Functional role and anatomic location of nitroxidergic nerves were determined in dog retinal arteries and arterioles. Isolated retinal central arteries responded to nicotine with relaxations that were not influenced by atropine, timolol, or indomethacin and damage of the endothelium, but were abolished by hexamethonium, methylene blue, and oxyhemoglobin. The relaxation was abolished by NG-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, and was restored by L-arginine. Relaxations caused by NO were not affected by L-NNA. Transmural electrical stimulation at 5 Hz relaxed the strips; the relaxation was abolished by L-NNA and tetrodotoxin. In anesthetized dogs, intraarterial injections of nicotine dilated retinal arterioles in the fundus oculi. This effect was abolished by L-NNA and restored by L-arginine. Intravenous injections of L-NNA constricted retinal arterioles, the effect being prevented by hexamethonium. There were nerve bundles and fibers containing NO synthase immunoreactivity in the adventitia and media in the retinal artery. These findings are consistent with our hypothesis that NO liberated from vasodilator nerves acts as neurotransmitter in dog retinal arteries and arterioles, and the arteriolar muscle tone is regulated by vasodilator nerve activity in vivo.

5-Hydroxytryptamine- and U46619-mediated vasoconstriction in bovine pulmonary conventional and supernumerary arteries: effect of endogenous nitric oxide

1999 ◽  
Vol 98 (1) ◽  
pp. 81-89 ◽  
Author(s):  
D. BUNTON ◽  
A. MACDONALD ◽  
T. BROWN ◽  
A. TRACEY ◽  
J. C. MCGRATH ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Guanylate Cyclase ◽  
Vascular Tone ◽  
No Synthase ◽  
Vasoconstrictor Response ◽  
Cgmp Pathway ◽  
Endogenous Nitric Oxide ◽  
Synthase Inhibitor ◽  
Resting Tone

We compared 5-hydroxytryptamine (5-HT)- and U46619-mediated contractions in bovine pulmonary conventional arteries (CA) and supernumerary arteries (SA). The effects of the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) (100 μM) and the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 μM) on the responses of CA and SA to 5-HT and U46619 were also examined. In addition, the effects of the 5-HT2B receptor antagonist SB 200646 (1 nM–1 μM) on the responses to 5-HT in SA and CA were studied. Tissue cGMP levels were measured in the absence and presence of l-NAME, ODQ, 5-HT and U46619. 5-HT was approximately 30 times more potent in SA {-log [EC50 (M)] (pEC50) 6.32±0.13} than in CA (5.05±0.14). U46619 displayed a similar potency in both CA (pEC50 7.80±0.07) and SA (7.75±0.12). l-NAME did not significantly alter the resting tone of CA or SA. In contrast, ODQ produced a transient increase in the tone of both CA and SA. Neither l-NAME nor ODQ altered the responses to 5-HT or U46619 in CA. In addition, neither l-NAME nor ODQ altered the responses to U46619 in SA, but both l-NAME and ODQ increased the magnitude of the response to 5-HT in SA without changing the sensitivity. Inhibition of the 5-HT2B receptor with SB 200646 did not alter the response to 5-HT in SA or CA. Basal levels of cGMP (pmol/mg of protein) were similar in CA (1.16±0.33) and SA (0.8±0.51), and were not significantly changed in the presence of 5-HT or U46619. l-NAME and ODQ reduced the basal levels of cGMP in both SA and CA. The results suggest that endogenous NO selectively attenuates the vasoconstrictor response to 5-HT in SA, but not in CA. These results also suggest that the NO/cGMP pathway may have a role in maintaining low vascular tone, but that other mechanisms are able to compensate for the absence of this pathway.

Endogenous nitric oxide influences acetylcholine-induced bronchovascular dilation in sheep

1995 ◽  
Vol 78 (2) ◽  
pp. 539-545 ◽  
Author(s):  
F. Sasaki ◽  
P. Pare ◽  
D. Ernest ◽  
T. Bai ◽  
L. Verburgt ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Vascular Tone ◽  
No Synthase ◽  
Pulmonary Resistance ◽  
Similar Extent ◽  
Maximal Increase ◽  
Endogenous Nitric Oxide ◽  
Synthase Inhibitor ◽  
Endothelial Nitric Oxide

To test whether endogenous endothelial nitric oxide (NO) influences baseline bronchial vascular tone and mediates acetylcholine (ACh)-induced bronchial vascular dilation and/or modulates bronchoconstriction in ovine airways, we studied anesthetized ventilated open-chest sheep and measured bronchial blood flow (Qbr) and pulmonary resistance (RL). In six sheep we measured the response of Qbr and RL to the dose of ACh required to produce 50% of the maximal increase in Qbr at baseline during infusion of the NO synthase inhibitor NG-nitro-L-arginine (L-NNA; 10(-2) M). Infusion of L-NNA decreased both the baseline Qbr (28 +/- 13 to 8 +/- 2 ml/min, P < 0.01) and the change in Qbr (delta Qbr) from the baseline value (84 +/- 42 to 33 +/- 18 ml/min, P < 0.05). There was no difference in baseline RL or in the response of RL to ACh at any time. In another six sheep, phenylephrine (5 x 10(-6) to 5 x 10(-7) M) decreased baseline Qbr (22 +/- 6 to 10 +/- 3 ml/min, P < 0.05) but not delta Qbr (62 +/- 13 to 66 +/- 21 ml/min, not significant). Infusion of L-NNA in these sheep decreased the baseline Qbr to a similar extent (11 +/- 5 ml/min) and also decreased delta Qbr (42 +/- 16 ml/min, P < 0.05). We conclude that endogenous endothelial NO influences baseline vascular tone and ACh-induced vasodilation of the ovine bronchial vasculature but has no effect on baseline RL or ACh-induced bronchoconstriction.

Vasoactivity of the gasotransmitters hydrogen sulfide and carbon monoxide in the chicken ductus arteriosus

2011 ◽  
Vol 301 (4) ◽  
pp. R1186-R1198 ◽  
Author(s):  
Saskia van der Sterren ◽  
Pamela Kleikers ◽  
Luc J. I. Zimmermann ◽  
Eduardo Villamor
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Guanylate Cyclase ◽  
Vascular Tone ◽  
Soluble Guanylate Cyclase ◽  
Ductus Arteriosus ◽  
No Synthase ◽  
Mechanical Responses ◽  
Synthase Inhibitor

Besides nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H2S) is a third gaseous messenger that may play a role in controlling vascular tone and has been proposed to serve as an O2 sensor. However, whether H2S is vasoactive in the ductus arteriosus (DA) has not yet been studied. We investigated, using wire myography, the mechanical responses induced by Na2S (1 μM–1 mM), which forms H2S and HS− in solution, and by authentic CO (0.1 μM-0.1 mM) in DA rings from 19-day chicken embryos. Na2S elicited a 100% relaxation (pD2 4.02) of 21% O2-contracted and a 50.3% relaxation of 62.5 mM KCl-contracted DA rings. Na2S-induced relaxation was not affected by presence of the NO synthase inhibitor l-NAME, the soluble guanylate cyclase (sGC) inhibitor ODQ, or the K+ channel inhibitors tetraethylammonium (TEA; nonselective), 4-aminopyridine (4-AP, KV), glibenclamide (KATP), iberiotoxin (BKCa), TRAM-34 (IKCa), and apamin (SKCa). CO also relaxed O2-contracted (60.8% relaxation) and KCl-contracted (18.6% relaxation) DA rings. CO-induced relaxation was impaired by ODQ, TEA, and 4-AP (but not by l-NAME, glibenclamide, iberiotoxin, TRAM-34 or apamin), suggesting the involvement of sGC and KV channel stimulation. The presence of inhibitors of H2S or CO synthesis as well as the H2S precursor l-cysteine or the CO precursor hemin did not significantly affect the response of the DA to changes in O2 tension. Endothelium-dependent and -independent relaxations were also unaffected. In conclusion, our results indicate that the gasotransmitters H2S and CO are vasoactive in the chicken DA but they do not suggest an important role for endogenous H2S or CO in the control of chicken ductal reactivity.

Identification of neutrophil chemotactic factors in bronchoalveolar lavage fluid of asthmatic patients

1997 ◽  
Vol 27 (4) ◽  
pp. 396-405 ◽  
Author(s):  
L. M. TERAN ◽  
M. G. CAMPOS ◽  
B. T. BEGISHVILLI ◽  
J.-M. SCHRODER ◽  
R. DJUKANOVIC ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Asthmatic Patients ◽  
Chemotactic Factors
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