Modulation of airway responses by prostaglandins in young and fully grown rabbits

2007 ◽  
Vol 293 (1) ◽  
pp. L239-L244 ◽  
Author(s):  
Gary L. Larsen ◽  
Joan Loader ◽  
Cori Fratelli ◽  
June-ku Brian Kang ◽  
Azzeddine Dakhama ◽  
...  
Keyword(s):  
Electrical Field Stimulation ◽  
Prostaglandin E ◽  
Neurokinin A ◽  
Response Curves ◽  
Electrical Field ◽  
New Zealand White Rabbits ◽  
Prostaglandin F ◽  
Prostaglandin Inhibitor ◽  
Airway Responses ◽  
Airway Tone

Maturational changes have been noted in neurally mediated contractile and relaxant responses in airways from New Zealand White rabbits. In this study, we focused on prostaglandins with bronchoprotective properties as potential modulators of airway tone in maturing rabbits. Tracheal rings from 1-, 2-, and 13-wk-old rabbits were assessed for neurally mediated contractile and relaxant responses produced by electrical field stimulation (EFS) of nerves in the presence and absence of the prostaglandin inhibitor, indomethacin (Indo). We also measured EFS-induced release of prostaglandin E2 (PGE2) and the stable metabolite of prostacyclin, 6-keto-prostaglandin F1α (6-keto-PGF1α). In the presence of Indo, EFS produced significant increases in contractile responses in segments from 1- and 2-wk-old animals but not in segments from 13-wk adult rabbits. Tracheal rings from 1- and 2-wk-old animals precontracted with neurokinin A (NKA) relaxed 100% in response to EFS when Indo was not in the bath. In rings from 13-wk-old animals, relaxation was 40%. With Indo, relaxation was abolished in 1-wk-old animals and reduced to 30% in the 2- and 13-wk-old groups. Buffer from baths collected after EFS had significant increases in PGE2 and 6-keto-PGF1α released from tissues from 1- vs. 2- and 13-wk-old animals. Dose response curves to PGE2 using tissues precontracted to NKA showed significant increases in relaxant responses in 1- and 2- vs. 13-wk-old rabbits. In rabbit airways, this study demonstrates enhanced modulation of airway tone by PGE2 and greater release of the bronchoprotective prostaglandins PGE2 and prostacyclin early in life.

Maturation of nonadrenergic noncholinergic inhibitory system in normal and allergen-sensitized rabbits

1994 ◽  
Vol 267 (6) ◽  
pp. L739-L744 ◽  
Author(s):  
G. N. Colasurdo ◽  
J. E. Loader ◽  
J. P. Graves ◽  
G. L. Larsen
Keyword(s):  
Electrical Field Stimulation ◽  
Neurokinin A ◽  
Inhibitory System ◽  
Electrical Field ◽  
New Zealand White Rabbits ◽  
Parenteral Exposure ◽  
The Mean ◽  
Nanc Relaxation ◽  
Specific Allergen

We investigated the functional existence of the nonadrenergic noncholinergic inhibitory (NANCi) system in developing rabbit airways in vitro. Furthermore, we evaluated the effect of parenteral exposure to a specific allergen (ragweed) on the maturation of this neural pathway. NANCi responses were studied on tracheal smooth muscle (TSM) segments obtained from normal and ragweed-sensitized New Zealand White rabbits at 1, 2, 4, and 12 wk of age. The TSM segments were removed and placed in tissue baths containing modified Krebs-Henseleit solution, atropine (1 x 10(-5) M), and propranolol (5 x 10(-6) M). After contraction with neurokinin A (1 x 10(-5) M), electrical field stimulation was applied at stimulation frequencies ranging from 5 to 30 Hz to determine the frequency that produced maximal relaxation. The NANCi response to EFS was measured and expressed as the mean (+/- SE) percent relaxation at 20 Hz, because this stimulation frequency gave the maximal NANCi response at each age studied. TSM segments obtained from control rabbits at 1 wk of age did not demonstrate a NANCi response at the frequencies of stimulation used. By contrast, a reproducible NANC relaxation was demonstrated in TSM from 2-, 4-, and 12-wk-old rabbits. The magnitude of this response was 27 +/- 4.7 (n = 10), 29 +/- 4.8 (n = 9), and 37 +/- 4% (n = 18), respectively. The same experiments performed on TSM segments obtained from ragweed-sensitized animals gave significantly decreased values of NANCi response. In 2-, 4-, and 12-wk-old rabbits, the NANCi responses were 11.5 +/- 3.4 (n = 9), 11 +/- 2 (n = 13), and 16 +/- 4.2% (n = 14).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of maturation on constrictive response to stimulation of C-fiber afferents in isolated guinea pig airways

2004 ◽  
Vol 287 (1) ◽  
pp. L168-L175 ◽  
Author(s):  
Z.-X. Wu ◽  
Q. H. Yang ◽  
T. Ruan ◽  
L.-Y. Lee
Keyword(s):  
Substance P ◽  
Guinea Pigs ◽  
Main Bronchus ◽  
Electrical Field Stimulation ◽  
Neurokinin A ◽  
Field Stimulation ◽  
Response Curves ◽  
Electrical Field ◽  
C Fiber ◽  
Stimulation Of

We investigated whether the airway constrictive response to stimulation of bronchopulmonary C-fiber afferents is altered during the maturation process. Isometric tension was measured in airway rings isolated from three tracheobronchial locations (intrathoracic trachea and main and hilar bronchi) and compared in mature [M, 407 ± 10 (SE) g body wt, n = 36] and immature (IM, 161 ± 5 g body wt, n = 35) guinea pigs. Our results showed no difference in the ACh (10−5 M)- or KCl (40 mM)-induced contraction between M and IM groups, regardless of the airway location. In sharp contrast, the concentration-response curves of 10−8–10−6 M capsaicin were distinctly lower in IM hilar bronchi; for example, response to the same concentration of capsaicin (10−6 M) was 89.2 ± 15.3% of the response to 10−5 M ACh in IM and 284.7 ± 43.2% in M animals. Similar, but smaller, differences in the bronchoconstrictive response to capsaicin between IM and M groups were also observed in the trachea and main bronchus. Electrical field stimulation induced airway constriction in all three locations in M and IM groups. However, after administration of 10−6 M atropine and 10−6 M propranolol, electrical field stimulation-induced contraction was significantly smaller in the hilar bronchus of IM than M animals, and this difference was not prevented by pretreatment with 5 × 10−5 M indomethacin. Although radioimmunoassay showed no difference in the tissue content of substance P between M and IM airways, the constrictive responses to exogenous substance P and neurokinin A were markedly greater in M airways at all three locations. In conclusion, the constriction of isolated airways evoked by C-fiber stimulation was significantly weaker in the IM guinea pigs, probably because of a less potent effect of tachykinins on the airway smooth muscle.

Substance P enhances electrical field stimulation-induced mast cell degranulation in rat trachea

1996 ◽  
Vol 270 (6) ◽  
pp. L985-L991 ◽  
Author(s):  
X. Y. Hua ◽  
S. M. Back ◽  
E. K. Tam
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Substance P ◽  
Electrical Field Stimulation ◽  
Mast Cell Degranulation ◽  
Facilitatory Effect ◽  
Neurokinin A ◽  
Field Stimulation ◽  
Cell Secretion ◽  
Electrical Field

We previously demonstrated in an ex vivo rat tracheal model that chymotryptic activity is an index of mast cell degranulation and that substance P (SP) and electrical field stimulation (EFS) synergistically degranulate mucosal and connective tissue mast cells. In the current study, we found that the facilitatory effect of SP was apparent at concentrations as low as 10(-9) M. This effect was mimicked by 10(-7) M neurokinin A or by 10(-6) M capsaicin and was blocked by the NK1 receptor antagonist CP-96,345. SP + EFS-induced mast cell secretion was significantly attenuated by 10(-6) M tetrodotoxin. The response was also attenuated in tracheas from rats in which sensory nerves had been depleted by systemic pretreatment with capsaicin or in which sympathetic nerves had been depleted by systemic pretreatment with 6-hydroxy-dopamine. Atropine (10(-6) M) or indomethacin (10(-5) M) also attenuated SP + EFS-induced mast cell secretion. Our findings suggest the importance of a sensitizing rather than a direct stimulating effect of SP on mast cell degranulation. SP may increase the sensitivity of mast cells to EFS-discharged mediators or facilitate the release of mast cell-stimulating mediators from autonomic nerves.

Effect of streptozotocin diabetes on motor and inhibitory transmission in rat anococcygeus

1992 ◽  
Vol 70 (10) ◽  
pp. 1372-1378 ◽  
Author(s):  
G. N. Luheshi ◽  
M. A. Zar
Keyword(s):  
Matched Control ◽  
Streptozotocin Diabetes ◽  
Electrical Field Stimulation ◽  
Diabetic Rats ◽  
Field Stimulation ◽  
Response Curves ◽  
Electrical Field ◽  
Contractile Responses ◽  
Inhibitory Transmission ◽  
Adrenergic Transmission

The effect of streptozotocin diabetes of 4-week duration on the adrenergic motor transmission and on the nonadrenergic, noncholinergic, inhibitory transmission in the rat anococcygeus was investigated by recording contractile and relaxant activity of isolated muscle preparations taken from diabetic and age-matched control animals. The neurogenic contractile responses to electrical field stimulation were significantly reduced in the preparations from diabetic rats. The inhibitory transmission remained unaffected in the diabetic rats. Concentration–response curves showed no change in sensitivity of the diabetic anococcygei to noradrenaline. The maximum tension generated was also similar in preparations from diabetic and nondiabetic animals. The contractile responses to electrical field stimulation were significantly greater in preparations from diabetic rats treated for 4 weeks with either sorbinil (20 mg∙kg−1∙day−1 orally) or myo-inositol (667 mg∙kg−1∙day−1 orally) when compared with the untreated diabetic controls; the sensitivity to noradrenaline was identical in all three groups. It is concluded that streptozotocin diabetes causes a significant reduction of adrenergic contractile responses of the anococcygeus to electrical field stimulation by a prejunctional mechanism, and the reduction can be prevented by treating the animals with the aldose reductase inhibitor sorbinil or with myo-inositol.Key words: streptozotocin; autonomic neuropathy; adrenergic transmission; nonadrenergic, noncholinergic transmission; sorbinil; myo-inositol.

Isovolumetric and isobaric rabbit tracheal contraction in vitro

1987 ◽  
Vol 62 (1) ◽  
pp. 82-90 ◽  
Author(s):  
R. H. Moreno ◽  
J. C. Hogg ◽  
T. M. McLean ◽  
P. D. Pare
Keyword(s):  
Electrical Field Stimulation ◽  
Organ Bath ◽  
Electrical Field ◽  
Optimal Length ◽  
New Zealand White Rabbits ◽  
Residual Capacity ◽  
Supramaximal Stimulation ◽  
Active Change

Isovolumetric and isobaric tracheal smooth muscle (TSM) contraction were studied in vitro in a preparation of the whole rabbit trachea. Eight tracheae from New Zealand White rabbits were excised and mounted at a fixed length in an organ bath. Electrical field stimulation (EFS) was performed in isovolumetric and isobaric conditions at varying transmural pressures (TMP). Supramaximal stimulation with methacholine was done at 0 TMP. Active change in pressure (delta P) with EFS showed a peak at 3.1 +/- 1.06 cmH2O TMP during inflation and at 4.1 +/- 1.18 cmH2O TMP during deflation (mean +/- SE). Active delta P decreased at higher or lower TMP. Active change in volume with EFS showed a peak at 3.2 +/- 1.26 cmH2O TMP during inflation and at 1.8 +/- 0.98 cmH2O TMP during deflation. A decrease in response was also observed at higher and lower TMP. From these data, we concluded that TSM is at optimal length (Lmax) at TMP of 2–3 cmH2O. Maximal TSM shortening with supramaximal stimulation with methacholine was 32% Lmax. This figure is considerably smaller than the 80% shortening found in unloaded strips of TSM. We conclude that rabbit TSM length is close to Lmax at TMP similar to those found at functional residual capacity and that the loads that the muscle has to overcome probably contribute to the limited shortening observed in situ.

scholarly journals Role of intrinsic airway neurons in ozone-induced airway hyperresponsiveness in ferret trachea

2001 ◽  
Vol 91 (1) ◽  
pp. 371-378 ◽  
Author(s):  
Zhong-Xin Wu ◽  
David F. Maize ◽  
Brian E. Satterfield ◽  
David G. Frazer ◽  
Jeff S. Fedan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Electrical Field Stimulation ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Field Stimulation ◽  
Electrical Field ◽  
Cholinergic Agonists ◽  
Airway Responses

Exposure to ozone (O3) enhances airway responsiveness, which is mediated partly by the release of substance P (SP) from airway neurons. In this study, the role of intrinsic airway neurons in O3-induced airway responses was examined. Ferrets were exposed to 2 ppm O3 or air for 1 h. Reactivity of isolated tracheal smooth muscle to cholinergic agonists was significantly increased after O3 exposure, as were contractions to electrical field stimulation at 10 Hz. Pretreatment with CP-99994, a neurokinin type 1 receptor antagonist, partially abolished the O3-induced reactivity to cholinergic agonists and electrical field stimulation. The O3-enhanced airway responses were present in tracheal segments cultured for 24 h, a procedure shown to deplete sensory nerves while maintaining viability of intrinsic airway neurons, and all the enhanced smooth muscle responses were also diminished by CP-99994. Immunocytochemistry showed that the percentage of SP-containing neurons in longitudinal trunk and the percentage of neurons innervated by SP-positive nerve fibers in superficial muscular plexus were significantly increased at 1 h after exposure to O3. These results suggest that enhanced SP levels in airway ganglia contribute to O3-induced airway hyperresponsiveness.

Modulation of acetylcholine release in rabbit airways in vitro

1995 ◽  
Vol 268 (3) ◽  
pp. L432-L437 ◽  
Author(s):  
G. N. Colasurdo ◽  
J. E. Loader ◽  
J. P. Graves ◽  
G. L. Larsen
Keyword(s):  
Regional Differences ◽  
High Performance ◽  
Acetylcholine Release ◽  
Electrical Field Stimulation ◽  
Nk1 Receptor ◽  
Ach Release ◽  
Electrical Field ◽  
Cholinergic Neurotransmission ◽  
New Zealand White Rabbits

We investigated the effects of substance P (SP) and vasoactive intestinal peptide (VIP) on acetylcholine (ACh) released from nerve endings by electrical field stimulation (EFS) in rabbit airways in vitro. ACh release was directly measured using high-performance liquid chromatography with electrochemical detection. Airway smooth muscle (ASM) segments, dissected from the midtrachea down to the left mainstem bronchus, were obtained from New Zealand White rabbits and mounted in organ baths containing modified Krebs-Henseleit solution, physostigmine, and choline. EFS at 20 Hz was delivered for 15 min to define baseline ACh release (pmol per gram of tissue per minute). There were no significant regional differences in ACh release during these baseline studies. A second stimulation was then performed in the absence (control) and presence of one or more of the following substances: SP (10(-7) M), a nonpeptide antagonist of the NK1 receptor (10(-7) M CP-96,345; Pfizer), and VIP (10(-7) M). Results for ACh release are expressed as a percentage of the first stimulation (means +/- SE). SP significantly increased ACh release in all ASM segments. This effect was abolished by CP-96,345. VIP alone did not affect ACh release. However, it significantly decreased SP-induced ACh release in all ASM segments. We conclude that SP significantly increases ACh release, thus facilitating cholinergic neurotransmission; its effect is abolished by CP-96,345. VIP decreases SP-induced ACh release, indicating a modulatory effect on cholinergic neurotransmission.

Maturation of acetylcholinesterase expression in tracheal smooth muscle contraction

1990 ◽  
Vol 259 (2) ◽  
pp. L130-L135 ◽  
Author(s):  
R. W. Mitchell ◽  
T. M. Murphy ◽  
E. Kelly ◽  
A. R. Leff
Keyword(s):  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Smooth Muscle Contraction ◽  
Tracheal Smooth Muscle ◽  
Maximal Response ◽  
Response Curves ◽  
Electrical Field ◽  
Stimulus Response ◽  
Cholinergic Contraction

We examined postganglionic development of acetylcholinesterase (AChase) activity and tracheal smooth muscle (TSM) contraction elicited by cholinomimetic activation and electrical field depolarization in vitro. Epithelium-intact tracheal strips excised from 21 2-wk-old swine (2ws) and 19 10-wk-old swine (10ws) were tethered isometrically at optimal resting length, and responses were expressed as percent of the maximum to 63 mM potassium-chloride (%KCl). Cumulative concentration-response curves to KCl were equivalent for TSM from 2 and 10ws. However, maximal contraction to ACh in 2ws (168 +/- 8.4 %KCl) was greater than for 10ws (142 +/- 2.3 %KCl; P less than 0.02). Stimulus-response curves (field electrodes; AC source) demonstrated greater sensitivity for TSM in 10ws (stimulus causing 50% of the maximal response = 3.32 +/- 0.13 V in 2ws vs. 2.25 +/- 0.12 V in 10ws; P less than 0.001), indicating that the greater cholinomimetic responsiveness of 2ws did not result from augmented presynaptic nerve conduction. The AChase inhibitor, physostigmine, caused 1) greater sensitivity of responses elicited by electrical field stimulation in 2ws (P less than 0.05) but not in 10ws (P = NS), 2) augmentation of maximal responses to exogenous ACh in 10ws (27% increase; P less than 0.01) but not 2ws (2% increase; P = NS), and 3) a greater increase in sensitivity to cholinomimetic activation in 2ws compared with 10ws (P less than 0.02). These data demonstrate increased cholinergic contraction of TSM in 2 vs. 10ws that results at least in part from reduced AChase activity in the trachea of immature animals.

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