Biomedical subjects

N E Robinson

Publications and source records attributed to N E Robinson.

At least 19 recordsLinked to original sources

PubMed1995

Prejunctional muscarinic autoreceptors on horse airway cholinergic nerves.

Muscarinic autoreceptors on horse airway cholinergic nerves were studied by examining the effects of muscarinic receptor antagonists on electrical field stimulation (EFS)-induced acetylcholine (ACh) release in trachealis preparations. All the antagonists including atropine (non-selective), pirenzepine (M1-selective), AF-DX 116 (M2-selective), and hexahydrosiladifenidol (M3-selective) augmented ACh release concentration-dependently. The augmentation was not due to displacement of ACh molecules from tissue receptors into the bath liquid because incubation with atropine after EFS had no influence on the measured amount of ACh. Hexahydrosiladifenidol was more potent in inhibiting ACh-induced muscle contraction, which is known to be mediated by M3 receptors, than in augmenting ACh release. The maximal ACh release rate in response to the selective antagonists was much less than that following atropine. Furthermore, the concentrations of the selective antagonists required to augment ACh release far exceeded their KdS for M1, M2, or M3 receptors. These observations suggest that the muscarinic autoreceptors on horse airway cholinergic nerves may belong to a novel subtype.

Acetylcholine↗

PubMed1995

Catecholamine affects acetylcholine release in trachea: alpha 2-mediated inhibition and beta 2-mediated augmentation.

We investigated the effects of catecholamines on acetylcholine (ACh) release from equine airway parasympathetic nerves. Trachealis strips were suspended in 2-ml tissue baths with Krebs-Henseleit solution containing atropine (10(-7) M), neostigmine (10(-6) M), and guanethidine (10(-5) M). Electrical field stimulation (20 V, 0.5 ms, 0.5 Hz, for 15 min) was applied, and ACh was measured by high-performance liquid chromatography with electrochemical detection. Epinephrine (Epi) and norepinephrine (NE) inhibited ACh release in a concentration-dependent manner. Inhibition was attenuated by the alpha 2-adrenoceptor antagonist idazoxan (10(-6) M) but not by the alpha 1-antagonist prazosin (10(-6) M). After alpha 2-blockade with idazoxan (10(-5) to 10(-4) M), Epi but not NE augmented ACh release. Isoproterenol (10(-7) to 10(-5) M) increased ACh release, an effect that was reversed by the beta 2-adrenoceptor antagonist ICI-118,551 (10(-5) M) but not by the beta 1-adrenoceptor antagonist atenolol (10(-5) M). Our results indicate that horse airway cholinergic nerves are modulated by both alpha 2-inhibitory and beta 2-excitatory adrenoceptors, with the former being predominant.

Acetylcholine↗

PubMed1995

Beta 2-adrenoceptor activation augments acetylcholine release from tracheal parasympathetic nerves.

We determined the effects of isoproterenol (Iso) on parasympathetic neurotransmission in isolated equine trachealis strips by comparing the effects of Iso on the contractile response to electrical field stimulation (EFS) and acetylcholine (ACh), as well as by measuring EFS-induced ACh release. The interaction of Iso with muscarinic receptors and endogenous nitric oxide was also investigated. ACh release was measured by high-performance liquid chromatography with electrochemical detection. Iso (10(-7) M or greater) caused significantly more inhibition of EFS- than of ACh-induced contraction, an observation usually interpreted as evidence of prejunctional inhibition of ACh release. However, the latter conclusion was not supported by measurement of ACh release. Iso concentration dependently augmented ACh release, which was reversed by the beta 2-adrenoceptor antagonist ICI-118,551 but not by the beta 1-adrenoceptor antagonist CGP-20,712A. Our results indicate that activation of beta 2-adrenoceptors augments ACh release. Moreover, the comparison of inhibitory effects on EFS- and ACh-induced contraction does not provide correct information about the prejunctional actions of beta-agonists. ACh release was increased more by atropine (10(-7) M) than by Iso (10(-6) M), indicating the predominance of prejunctional inhibitory muscarinic autoreceptors over excitatory beta 2-adrenoceptors. Additionally, we found that inhibition of nitric oxide synthase by NG-nitro-L-arginine did not affect either the cholinergic contractile response or ACh release in both the absence and presence of Iso.

Acetylcholine↗

PubMed1995

Acetylcholine release from airway cholinergic nerves in horses with heaves, an airway obstructive disease.

The present study was conducted to determine if acetylcholine (ACh) release from airway cholinergic nerves is increased and if modulation of ACh release by prejunctional receptors is altered in horses with heaves, an obstructive airway disease characterized by airway inflammation and bronchospasm. Trachealis strips and bronchial segments of normal horses and horses affected with heaves were suspended in 2-ml tissue baths. ACh release was induced by electrical field stimulation and the bath ACh content was measured by high performance liquid chromatography (HPLC) with electrochemical detection. In response to electrical field stimulation, the rate of ACh release from cholinergic nerves innervating the trachea was not significantly different between the two groups of horses. The nonselective muscarinic receptor antagonist atropine augmented ACh release to the same extent in both groups, indicating that there is no dysfunction of muscarinic autoreceptors on cholinergic nerves of large airways from horses with heaves. Compared with the data from normal horses, the inhibitory effect of the alpha 2-adrenoceptor agonist clonidine on ACh release was lacking in the bronchi and less potent in the trachea, suggesting that the prejunctional alpha 2-adrenoceptors are dysfunctional in horses with heaves. Neither exogenous prostaglandin E2 (PGE2) nor the cyclooxygenase inhibitor indomethacin influenced ACh release from the bronchi, suggesting that a decrease in airway mucosal PGE2 production reported previously in horses with heaves does not alter ACh release.

Acetylcholine↗

PubMed1995

Definition of chemiluminescence and superoxide production responses of bovine neutrophils to selected soluble and particulate stimulants, and comparisons with the responses to Pasteurella haemolytica.

We defined methods for use of luminol-dependent chemiluminescence (LDCL) and superoxide anion (O2-) production as parameters of the oxidative metabolism of neutrophils isolated from 1.5- to 5-week-old neonatal calves. We determined how variations in blood sample handling, agonist preparation, individual variability, and age of calves influenced the LDCL and O2- responses to certain agonists, and defined concentrations of soluble and particulate agonists that maximally stimulated the oxidative metabolism of bovine neutrophils. Oxidative responses, particularly LDCL, were characterized by marked day-to-day variability, differed greatly within and between calves, were partially age-dependent, and were partially dependent on the individual agonist. Superoxide anion production had substantially less variability. We compared the in vitro oxidative (LDCL and O2-) responses of neutrophils isolated from neonatal calves stimulated by defined concentrations of the agonists--latex, phorbol myristate acetate, calcium ionophore, and opsonized zymosan--with responses to formylated oligopeptides and zymosan-activated serum, and to live, dead, live opsonized, and dead opsonized Pasteurella haemolytica organisms. Opsonization of particulates, pathogenic or nonpathogenic, enhanced the LDCL and O2- responses of stimulated neutrophils although P haemolytica was a less potent stimulant of oxidative functions than were nonbiological agonists. We conclude that the generation of reactive oxygen species by bovine neutrophils in response to P haemolytica is highly dependent on the presence of opsonins and is greatly enhanced in live vs killed bacteria. Furthermore, the in vitro generation of reactive oxygen species, including O2- by stimulated neutrophils, may be of biologic importance if similar events occur in vivo, and could have a major role in the pathogenesis of the acute lung injury associated with pneumonic pasteurellosis.

Adjuvants, Immunologic↗

PubMed1995

Enzyme release by bovine neutrophils.

Release of enzymes from cytoplasmic granules has been postulated to have a major role in neutrophil-mediated tissue injury. Secretion or release of primary granules, specific granules, and cytosolic enzymes by bovine neutrophils was examined by quantifying the release of beta-glucuronidase, B12-binding protein, and lactate dehydrogenase, respectively, in response to predetermined amounts of phorbol myristate acetate, calcium ionophore, and opsonized zymosan. These responses were compared with the enzyme release induced by exposure to live or dead, unopsonized or opsonized Pasteurella haemolytica. The greatest release of beta-glucuronidase, B12-binding protein, and lactate dehydrogenase was observed in neutrophils exposed to live organisms partially because of neutrophil lysis. Bovine neutrophils respond markedly to particulate agonists, live or dead, pathogenic or nonpathogenic, by a selective release of specific granules, an effect enhanced by opsonization. Particulate agonists induce minimal primary granule release other than that induced by cell death. Because bovine neutrophils contain quantitatively high numbers of specific granules, the high rate of secretion/release in response to P haemolytica organisms could have a major role in the tissue responses that characterize the lesions of pneumonic pasteurellosis.

Analysis of Variance↗

PubMed1994

Distribution of SP- and CGRP-like immunoreactive nerve fibers in the lower respiratory tract of neonatal foals: evidence for loss during development.

The lungs of neonatal foals contain many nerves immunoreactive for substance P and calcitonin gene-related peptide. These nerves are closely associated with the epithelium, bronchial and pulmonary vessels and the airway smooth muscle of all intrathoracic airways, including non-cartilaginous bronchioles. Activation of sensory nerves in the respiratory epithelium could thus potentially affect, via local axon reflexes, vascular and respiratory smooth muscle in neonatal equine airways. Nerves immunoreactive for these peptides are much more widely distributed within the lung than in adult horses; they may thus play a trophic role before birth, or contribute to the post-natal adaptation to breathing.

Animals↗

PubMed1994

PGE2 inhibits acetylcholine release from cholinergic nerves in canine but not equine airways.

The effects of exogenous prostaglandin E2 (PGE2) and endogenous prostanoids on cholinergic neurotransmission were determined by measurement of acetylcholine (ACh) release from canine and equine airway tissues. Trachealis strips and bronchial segments were suspended in 2 ml tissue baths. ACh release was induced by electrical field stimulation (EFS), and its content in tissue bath liquid was measured by high pressure liquid chromatography (HPLC) with electrochemical detection. In canine airways, exogenous PGE2 (10(-9) to 10(-7) M) inhibited ACh release concentration-dependently, whereas inhibition of endogenous prostanoid production by indomethacin (3 x 10(-6) M) augmented ACh release. By contrast, in equine airways, exogenous PGE2 had no effect on ACh release in bronchi but at 10(-7) M augmented ACh release in the trachea. Cyclooxygenase inhibition by either indomethacin or meclofenamate (10(-6) M) did not influence ACh release. We conclude that exogenous PGE2 and endogenous prostanoids inhibit ACh release from cholinergic nerves in canine but not equine airways.

Acetylcholine↗

PubMed1994

Expression of fucosylated antigens and alpha 1,3 fucosyltransferases in human leukaemia cell lines.

The expression of alpha 1,3 fucosylated type 2 antigens is generally thought to be restricted to myeloid cells among normal human haemopoietic tissue. The distribution of three fucosylated antigens [Lewis X (Le(x)), sialyl Lewis X (sLex) and VIM2] was investigated among nine human leukaemia cell lines by fluorescence activated cell sorting (FACS) analysis. As expected, all myeloid cell lines were positively stained by antibodies against these three fucosylated antigens. Unexpectedly, two T-lymphocytic cell lines (CCRF-CEM and MOLT4) were found to express Le(x) and VIM2, and the plasma, B-cell line, RPMI 8226, expressed all three fucosylated antigens. Enzymatic and RNA analyses [Northern blot and reverse transcription polymerase chain reaction (RT-PCR)] were used to evaluate possible control points in the biosynthetic pathway for Le(x) and sLex. beta 1,4 Galactosyltransferase (beta 1,4GalT, an enzyme involved in the synthesis of the core oligosaccharide of the three fucosylated antigens) activity and the corresponding mRNA were found in all of the leukaemia cell lines, regardless of whether or not they expressed the fucosylated antigens. In contrast, alpha 1,3 fucosyltransferase (GDP-fucose:beta-D-N-acetylglucosaminide 3-alpha-L-fucosyltransferase; alpha 1,3FT) activity and the corresponding mRNA were found only in those cell lines expressing fucosylated antigens. Based on RNA analysis, acceptor specificity and N-ethylmaleimide inhibition studies, it was concluded that all of the cell lines expressing fucosylated antigens contained alpha 1,3FTIV (myeloid alpha 1,3FT). This appeared to be the major alpha 1,3FT in the myeloid and T-lymphocytic cell lines. Interestingly, even though both types of cell lines expressed the same alpha 1,3FT, only the myeloid cell lines expressed sLex, whereas all of the myeloid and T-lymphocytic cell lines expressed a structural analogue of sLex (i.e. VIM2). In contrast to the myeloid and T-cell lines, RPMI 8226 cells contained more than one fucosyltransferase activity. Acceptor specificity analysis demonstrated that this cell line contains alpha 1,3 and alpha 1,4FTs. Among the fucosyltransferases expressed by RPMI 8226, alpha 1,3FTIV accounted for only a small amount of the total activity. The results of this study demonstrate that fucosylated antigens, which are generally considered to be myeloid specific antigens, are also expressed by lymphocytic leukaemia cell lines, and that the types of fucosylated antigens and fucosyltransferases expressed in these cell lines vary.

Antigens, Neoplasm↗

PubMed1994

Need for advanced cardiac life-support training in rural, community hospitals.

OBJECTIVE: To define the relative needs of the staffs of rural, community hospitals for training in advanced cardiac life support (ACLS), identify weaknesses, and modify a standard ACLS course to meet these needs. DESIGN: Prospective assessment of knowledge and skills relating to the practice of ACLS. SETTING: Rural, community hospitals in southern Wisconsin. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A well-validated, multiple-option, precourse test for life-support knowledge and clinical judgment was administered to the staff nurses, respiratory therapists, and practicing physicians of 12 rural, community hospitals in southern Wisconsin before their participation in a modified, extended, ACLS course, using the pre-1992 American Heart Association standards and guidelines. Testing was accomplished over 4 yrs. Detailed item analysis of the test was performed. A total of 461 persons participated. Overall, physicians performed better (p < .001) than did the nurses. Precourse difficulties included electrocardiographic rhythm strip interpretation, particularly with identification of the atrioventricular (A-V) blocks. Only 39.6% of the nurses and 64.1% of the physicians correctly identified third-degree A-V block. One third of the nurses and 22% of the physicians did not correctly identify coarse ventricular fibrillation. The pharmacologic properties and utility of atropine and epinephrine were not understood. Propranolol was selected for treatment of third-degree A-V block by 31.6% and 22.8% of the nurses and the physicians, respectively. Neither group was able to accurately distinguish between the components of disturbances in acid-base balance. The esophageal obturator airway tube was not a familiar tool to any of the groups. No improvement in overall performance on pretests occurred across the calendar years of the study. CONCLUSIONS: There is a need for ACLS training in community hospitals. Educational programs for physicians and staffs should be designed to meet that need.

Clinical Competence↗

PubMed1994

Effect of advanced cardiac life-support training in rural, community hospitals.

OBJECTIVES: To define the effectiveness of training personnel in rural, community hospitals in advanced cardiac life support (ACLS) and the changes that result in the process and quality of care to patients with ischemic heart disease that can be attributed to participation by team members in an ACLS course. DESIGN: Case-controlled, retrospective abstraction of hospital records of 869 consecutive patients with ischemic heart disease, who were admitted during the year preceding and the year following the ACLS course. SETTING: Seven rural, community hospitals in Wisconsin. SUBJECTS: Physicians, nurses, and other critical care staff (others). INTERVENTIONS: Training in ACLS using 12 3-hr sessions in an interdisciplinary format by a multidisciplinary faculty. MEASUREMENTS AND MAIN RESULTS: Rates of successful attainment of the terminal behavior objectives by physicians and nurses were 84.0% and 78.8%, respectively. Less than 50% of others achieved a satisfactory level of competence. Performance on an examination of cognitive ability improved significantly for all groups (p < .005 for nurses; p < .05 for physicians). Enhancement of knowledge base and integrative skills occurred in all areas of designated ACLS content. Difficulty remained apparent relative to the pharmacologic effects of epinephrine and atropine. No statistically significant deterioration in didactic knowledge base could be detected 1 to 2 yrs after completion of the ACLS course. Slight deterioration in intubation and defibrillation skills occurred in < 3 months after completion of the course. Substantial costs were encumbered by the hospitals, despite the free training provided to the institutions. After ACLS training had been given, overall mortality rates decreased from 17.4% to 13.4% (p < .05). A pooled estimate of the decrease in the mortality rate was 1.4 +/- 3.8%/quarter. Across the entire spectrum of severity of illness, the probabilities for survival increased at a given severity of illness following completion of the course (p = .06). When extremes of severity of illness were excluded from the analysis, the differences in probability for survival over the midrange of severity were statistically significant (p < .05). CONCLUSIONS: Training directed to the entire team likely to participate in the provision of ACLS in the community hospital favorably affects the overall practice of ACLS and the survival rate of patients with ischemic heart disease.

Aged↗

PubMed1994

Evaluation of partial arytenoidectomy as a treatment for equine laryngeal hemiplegia.

The efficacy of partial arytenoidectomy was assessed in 6 Standardbred horses, with surgically induced laryngeal hemiplegia, at rest (Period A) and during exercise at speeds corresponding to maximum heart rate (Period C) and 75% of maximum heart rate (Period B). Peak expiratory and inspiratory airflow rate (PEF and PIF), and expiratory and inspiratory transupper airway pressure (PUE and PUI) were measured and expiratory and inspiratory impedance (ZE and ZI) were calculated. Simultaneously, tidal breathing flow-volume loops (TBFVL) were acquired using a respiratory function computer. Indices derived from TBFVL included airflow rates at 50 and 25% of tidal volume (EF50, IF50, EF25, and IF25) and the ratios of expiratory to inspiratory flows. Measurements were made before left recurrent laryngeal neurectomy (baseline), 2 weeks after left recurrent laryngeal neurectomy (LRLN) and 16 weeks after left partial arytenoidectomy coupled with bilateral ventriculectomy (ARYT). After LRLN, during exercise Periods B and C, Z1 and the ratio of EF50/IF50 significantly increased and PIF, IF50 and IF25 significantly decreased from baseline values. At 16 weeks after ARYT, Z1 returned to baseline values during Periods B and C. Although PIF, IF50, IF25, PEF/PIF, and EF50/IF50 returned to baseline values during Period B, these indices remained significantly different from baseline measurements during Period C. After ARYT, TBFVL shapes from horses during Period C approached that seen at the baseline evaluation. Partial arytenoidectomy improved upper airway function in exercising horses with surgically induced left laryngeal hemiplegia, although qualitative and quantitative evaluation of TBFVLs suggested that some flow limitation remains at near maximal airflow rates. These results indicate that, although the procedure does not completely restore the upper airway to normal, partial arytenoidectomy is a viable treatment option for failed laryngoplasty and arytenoid chondropathy in the horse.

Animals↗

PubMed1994

Inhibitory nerve distribution and mediation of NANC relaxation by nitric oxide in horse airways.

The distribution of inhibitory nerves and the mediator of the inhibitory nonadrenergic noncholinergic (iN-ANC) nervous system were investigated in smooth muscle preparations from seven regions of equine airways. In tissues incubated with atropine and precontracted with histamine, electrical field stimulation produced frequency-dependent relaxation, and the magnitude of the relaxation decreased from trachea to central bronchi and was absent in peripheral airways. The degree of relaxation in bronchi was not simply a function of bronchial size or generation. Propranolol inhibited part of the relaxation only in the cranial trachealis. After propranolol, NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, eliminated the remaining relaxation in all preparations. This effect was reversed by L-arginine, the NO precursor, but not by D-arginine. Exogenous NO concentration dependently relaxed trachealis. These results indicate that: 1) adrenergic innervation is limited to cranial trachealis, 2) iNANC nerves supply the trachea and central bronchi, and 3) NO mediates iNANC function.

Animals↗

PubMed1994

Modulation of bronchial smooth muscle function in horses with heaves.

Four mechanisms that modulate airway smooth muscle function in normal horses were studied in the bronchi of horses affected by the airway obstructive disease heaves. Results were compared with data from historical controls studied by the same personnel in the same laboratory. Rings from the left cranial lobar bronchus (LB1) and small bronchi (5 mm OD) were suspended in muscle baths, and the isometric tension were measured. The inhibitory nonadrenergic noncholinergic (iNANC) function was studied in LB1. After the LB1 segments were pretreated with atropine and contracted with histamine, electrical field stimulation (EFS) induced little or no relaxation, indicating iNANC dysfunction in horses with heaves. Bronchi from animals with heaves were hyporesponsive to EFS and acetylcholine. Epithelial removal augmented the contractile response of small bronchi to acetylcholine more in animals with heaves than in control animals, indicating an enhanced function of epithelial-derived relaxing factor. In contrast, cyclooxygenase inhibition with meclofenamate (10(-6) M) increased the EFS-induced contraction of small bronchi less in affected horses than in control horses, suggesting a change in prostaglandin production in favor of excitatory prostanoids. We conclude that in the bronchi of horses with heaves; the iNANC function is defective, the response of smooth muscle to cholinergic activation is diminished, the production of epithelial-derived relaxing factor is enhanced, and the inhibitory function of prostanoids is reduced.

Acetylcholine↗

PubMed1994

Substance P and calcitonin gene-related peptide-like immunoreactive nerve fibers in lungs from adult equids.

Distribution of pulmonary nerves immunoreactive for either substance P or calcitonin gene-related peptide was determined, using immunohistochemical methods on healthy lungs from adult equids. The overall patterns of distribution of substance P and calcitonin gene-related peptide-like immunoreactivity were similar. Distribution of immunoreactive nerves was not uniform throughout the lungs; nerve fibers immunoreactive for these peptides were more frequently observed near the hilus of the lung than in the caudal lobes or in the periphery of the lung. Nerve fibers immunoreactive for substance P or calcitonin gene-related peptide were most abundant in the lamina propria of the trachea and larger airways, particularly within and directly below the airway epithelium; they were also frequently associated with bronchial and pulmonary vessels. Presence of nerve fibers immunoreactive for substance P and calcitonin gene-related peptide in peribronchial neural ganglia indicated that these sensory nerves may modulate parasympathetic regulation of pulmonary function. Nerve fibers immunoreactive for substance P and calcitonin gene-related peptide were, therefore, well placed to detect inhaled agents and to contribute to the pulmonary response to irritants and pathogens.

Afferent Pathways↗

PubMed1994

Tidal breathing flow-volume loops in horses with recurrent airway obstruction (heaves).

Tidal breathing flow-volume (TBFV) loops were determined in a group of control horses and in horses affected with recurrent airway obstruction (heaves). The latter group was studied when the condition was in remission and under increasing amounts of airway obstruction as reflected by measurements of change in pleural pressure, pulmonary resistance, and dynamic compliance. The TBFV loops of control horses had biphasic inspiratory and expiratory patterns; peak inspiratory and peak expiratory flows were detected early in inspiration and expiration, respectively. Tidal volume was unaffected by heaves, but at all stages of heaves, respiratory frequency was increased principally because of shorter inspiratory time, and therefore, inspiratory flow rate was increased. In horses with heaves, TBFV loops did not have a biphasic pattern; peak inspiratory flow was observed late in inspiration, and peak expiratory flow was observed early in expiration. As airway obstruction became more severe, peak expiratory flow increased as pulmonary resistance increased so that, during severe airway obstruction, TBFV loops had a characteristic appearance with high peak expiratory flow early in expiration followed by low flow rate.

Airway Obstruction↗

PubMed1993

Adrenergic and peptidergic innervation of the trachealis muscle in the normal horse: a preliminary report.

The tone of respiratory smooth muscle is largely determined by the input from autonomic nerves. The distribution of adrenergic and selected nonadrenergic, non-cholinergic (NANC) nerves in the normal equine trachealis muscle was investigated using immunohistochemistry. The smooth muscle of the trachealis was found to contain numerous nerves immunoreactive for an enzymatic marker of adrenergic nerves, as well as many nerves immunoreactive for a putative NANC neurotransmitter, peptide histidine isoleucine, a potent bronchodilator. The tissue surrounding the respiratory smooth muscle contained numerous nerves immunoreactive for the neuropeptides substance P and calcitonin gene-related peptide, which can cause marked vasodilation and bronchoconstriction. The complex innervation of the equine trachea should be kept in mind when interpreting the results of physiological experiments.

Animals↗

PubMed1993

Independent modulation of horse airway smooth muscle by epithelium and prostanoids.

The effects of epithelial removal and cyclooxygenase inhibition on contractions induced by exogenous acetylcholine (ACh) and electrical field stimulation (EFS) were evaluated in horse tracheal strips and bronchial rings. Epithelial removal potentiated the response to ACh but had no influence on the response to EFS. The effect of epithelial removal was not altered by pretreating the tissues with meclofenamate, a cyclooxygenase inhibitor. In trachealis strips, meclofenamate augmented contractions induced by EFS but not by ACh. In bronchial rings, meclofenamate augmented EFS-induced contraction to a greater extent than ACh-induced contraction. These effects of meclofenamate were epithelium-independent. We conclude that horse airway epithelium produces a relaxant factor that is not a prostanoid. Endogenous prostanoids originating from non-epithelial sites inhibit only cholinergic nerves in the trachea but both parasympathetic nerves and smooth muscle in the bronchi.

Acetylcholine↗