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Biomedical subjects

R Matran

Publications and source records attributed to R Matran.

At least 55 records · Page 3Linked to original sources
PubMed1990

Innervation of lower airways and neuropeptide effects on bronchial and vascular tone in the pig.

The occurrence and distribution of peptide-containing nerve fibres [substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), neuropeptide Y (NPY)] and noradrenergic nerve fibres [tyrosine hydroxylase (TH)- and dopamine beta hydroxylase (DBH)-positive] in the airways of the pig were studied by means of immunohistochemistry. SP- and CGRP-immunoreactive (-IR) nerve fibres were present close to and within the lining respiratory epithelium, around blood vessels, within the tracheobronchial smooth muscle layer and around local tracheobronchial ganglion cells. The content of CGRP- and neurokinin A (NKA)-like immunoreactivity (-LI) measured by radioimmunoassay (RIA) was twice as high in the trachea compared to that in the peripheral bronchi. SP was a more potent constrictor agent than NKA on pig bronchi in vitro. CGRP had a relaxant effect on precontracted pig bronchi. On blood vessels CGRP exerted a relaxant effect that was more pronounced on pulmonary arteries than on bronchial arteries. VIP/PHI-IR fibres were seen in association with exocrine glands and in the tracheobronchial smooth muscle layer. VIP-positive nerve fibres were abundant around blood vessels in the trachea but sparse or absent around blood vessels in the peripheral bronchi. This histological finding was supported by RIA; it was shown that the content of peptides displaying VIP-like immunoreactivity (-LI) was 18 times higher in the trachea compared to peripheral bronchi. VIP was equally potent as CGRP in relaxing precontracted pig bronchi in vitro. Both bronchial and pulmonary arteries were relaxed by VIP. NPY was colocalized with VIP in tracheal periglandular nerve fibres and in nerve fibres within the tracheobronchial smooth muscle layer. NPY was also present in noradrenergic (DBH-positive) vascular nerve fibres. The content of NPY was much higher (15-fold) in the trachea compared to small bronchi. NPY caused a contraction of both pulmonary and bronchial arteries. The bronchial smooth muscle contraction to field stimulation in vitro was purely cholinergic. A noncholinergic relaxatory effect following field stimulation was observed after bronchial precontraction. Capsaicin had no effect on pig bronchi in vitro.

Animals↗
PubMed1990

Cigarette smoke, nicotine and capsaicin aerosol-induced vasodilatation in pig respiratory mucosa.

1. Anesthetized pigs were used to study vascular responses in the sphenopalatine artery (SPA), superior laryngeal artery (SLA) and bronchial artery (BA) upon exposure to cigarette smoke or aerosol of nicotine and capsaicin. Direct blood flow recordings were made with ultrasonic probes around the vessels. 2. Smoke from one cigarette was administered as inhalation for 2 min with or without a Cambridge filter which removes the particulate matter including nicotine from the smoke. Aerosols of nicotine (2.5 mg) or capsaicin (10 mg) were administered to the nose or the lower airways for 3 min. 3. Cigarette smoke exposure caused a reproducible reduction of the vascular resistance (VR) suggesting vasodilatation in the SPA, SLA, and especially the BA. The vasodilatation was not modified by the Cambridge filter, suggesting that it was caused by vapour phase components rather than nicotine. 4. The smoke effect was not changed after pretreatment with the cyclo-oxygenase inhibitor, diclofenac, or with atropine, guanethidine, H1- or H2-histamine receptor antagonists, nedocromil, or by vagotomy. The smoke-evoked decrease in VR was not modified by the nicotinic receptor antagonist chlorisondamine in the SLA or BA. 5. In pigs pretreated with increasing doses of capsaicin two days earlier, the decrease in VR upon smoke exposure in both the BA and SLA was unaffected while the change in VR was attenuated in the SPA. 6. Nicotine aerosol had no effect on VR in the peripheral airways supplied by the BA while a decrease in VR was observed in the SLA and SPA. The nicotine response was reduced after capsaicin pretreatment in the nasal and upper tracheal circulation. 7. Capsaicin aerosol reduced VR in the vascular beds supplied by the SPA, SLA and BA and this response was markedly reduced after capsaicin pretreatment. 8. The mechanisms underlying vasodilatation upon cigarette smoke exposure in the bronchial mucosa are at the moment unclear while both non-cholinergic parasympathetic and sensory components may be involved in the nose. Capsaicin induced a vasodilatation at all levels via sensory mechanisms, whereas nicotine-evoked vasodilatation is restricted to the upper airway mucosa and is at least partly dependent on parasympathetic reflexes involving capsaicin-sensitive sensory nerves.

Aerosols↗
PubMed1990

Capsaicin and histamine antagonist-sensitive mechanisms in the immediate allergic reaction of pig airways.

The airway vascular and bronchial responses were studied in pigs sensitized with Ascaris suum. Ascaris, histamine (H) and capsaicin aerosol all induced a clear-cut increase in blood flow in the nasal, laryngeal and bronchial circulation with a decrease in vascular resistance of 20-40%. When delivered to the lung both ascaris and histamine, but not capsaicin, caused pulmonary airflow obstruction with increase in resistance and a fall in dynamic compliance of 40-70%. After pretreatment of pigs with a combination of the H1- and H2-receptor antagonists terfenadine and cimetidine, the vascular and bronchial responses were strongly reduced to both histamine (by greater than 77%) and ascaris (by greater than 58%), but not to capsaicin aerosol. The bronchoconstriction to histamine was found to be mediated by H1-receptors only, while both H1- and H2-antagonists were necessary to block the vasodilatory response, with H2-receptors being more important in the bronchial circulation and H1-receptors being more important in the laryngeal and nasal circulation. Furthermore, when pigs were pretreated with capsaicin systemically 2 days before the experiment, the vasodilation was decreased upon capsaicin (by 80%), ascaris (by greater than 40%) and histamine (by greater than 50%) aerosol challenge. When histamine was administered intravenously the desensitizing effect of capsaicin pretreatment was much less pronounced. The effect of capsaicin desensitization on the pulmonary obstruction upon ascaris and histamine challenge was limited to a 60% reduction of the fall in dynamic compliance and a delayed peak in resistance upon ascaris challenge. We conclude that histamine is one of the main vasodilatory mediators released upon allergen challenge at three different levels of the pig airways. A considerable part of the histamine effect is indirect and probably due to activation of capsaicin-sensitive sensory nerves.

Airway Obstruction↗
PubMed1990

Occurrence and effects of endothelin in guinea-pig cardiopulmonary tissue.

Endothelin-like immunoreactivity (-LI) was present in the guinea-pig cardiopulmonary tissues with the associated autonomic neural supply. The highest levels were found in the stellate ganglion (15 pmol g-1) followed by the vagus nerve, pulmonary artery, lung and right atrium of the guinea-pig. Endothelin I, but not endothelin III, induced an increase in contractile force and frequency followed by an atropine-resistant inhibition of right atrial contractility at higher concentrations. Exposure to endothelin I caused a pronounced, long-lasting coronary vasoconstriction as revealed by a decrease in perfusate outflow. In addition, both heart and contractile force were attenuated. Guinea-pig bronchi in vitro contracted upon exposure to endothelin I and III, but only endothelin I caused contraction of pulmonary arteries. The C-terminal hexapeptide of endothelin I did not influence right atrial, bronchial or pulmonary artery contractility. Endothelin I increased the mean arterial pressure and insufflation pressure and decreased the heart rate in the guinea-pig in vivo. In conclusion, endothelin-LI is present in the cardiovascular, respiratory and nervous tissues of the guinea-pig and endothelin induces strong coronary and pulmonary vasoconstrictor effects. The effects on atrial contractile force and frequency are concentration-dependent with stimulation at lower and inhibition at higher concentrations. Based on the diversity in response to endothelin III in the bronchi compared to atrium and pulmonary artery, it may be suggested that different receptor populations exist in bronchial and cardiovascular muscle, although the cellular localization and forms of endothelin present in guinea-pig cardiopulmonary tissue remain to be established.

Animals↗
PubMed1990

Local and central reflex mechanisms in the neural control of airway microcirculation.

Sensory and parasympathetic neural mechanisms play an essential role in the control of the microcirculation in the airway mucosa in response to inhalation of irritants and in local allergic reactions. Thus extravasation of plasma proteins is evoked by local release of peptides such as substance P (SP) from capsaicin-sensitive sensory nerves upon inhalation of cigarette smoke. Calcitonin gene-related peptide (CGRP) is another vasodilator agent which is also released from airway afferent nerves by capsaicin or antidromic nerve stimulation. Parasympathetic cholinergic and noncholinergic vasodilator mechanisms dominate in the nasal mucosa and trachea whereas the bronchial circulation is influenced mainly by local mechanisms involving mediator release from capsaicin-sensitive sensory nerves. The allergen-induced vasodilatation in the airway mucosa seems to a large extent to be caused by histamine which activates capsaicin-sensitive afferent nerves and evokes peptide release.

Animals↗
PubMed1989

Bronchial hyperresponsiveness to methacholine in patients with impaired left ventricular function.

To elucidate the pathogenesis of bronchospasm in congestive heart failure, we studied 23 patients with chronic impairment of left ventricular function due to coronary artery disease or dilated cardiomyopathy. In 21 of them we found marked bronchial hyperresponsiveness to methacholine. The mean dose (+/- SD) of methacholine that elicited a 20 percent decrease in the forced expiratory volume in one second (FEV1) was 421 +/- 298 micrograms, nearly the same as in patients with symptomatic asthma. In contrast, there was no bronchial response to methacholine in 9 of 10 patients who had coronary artery disease but normal left ventricular function. Administration of the bronchodilator albuterol led to a partial (43 percent) reversal of the methacholine-induced bronchial obstruction. In 12 patients, pretreatment with the alpha-adrenergic agonist methoxamine (10 mg by inhalation), a potent vasoconstrictor, fully prevented the methacholine-induced decrease in FEV1. The protective effect of methoxamine was blocked by the alpha-adrenergic antagonist phentolamine in all six patients who received this agent. We conclude that bronchial hyperresponsiveness to cholinergic agonists is frequent in patients with impaired left ventricular function and may contribute to the wheezy dyspnea commonly observed in such patients. The bronchoconstriction may be mediated at least in part by dilatation of the bronchial vessels.

Adult↗
PubMed1989

Inhibition of cholinergic and non-adrenergic, non-cholinergic bronchoconstriction in the guinea pig mediated by neuropeptide Y and alpha 2-adrenoceptors and opiate receptors.

The mechanisms underlying the regulatory influence of neuropeptide Y (NPY) and of alpha 2-adrenoceptor and opiate receptor activation on cholinergic and excitatory non-adrenergic, non-cholinergic (e-NANC) neurotransmission were studied in guinea pig hilus bronchi in vitro. NPY inhibited both the cholinergic and e-NANC bronchial contractions evoked by field stimulation. The NPY attenuation of the e-NANC contraction could not be antagonized by the alpha 2-antagonist, idazoxan, or naloxone. UK 14,304 a specific alpha 2-agonist, also reduced the two nervous components of bronchial contraction and this action was inhibited by idazoxan. NPY and UK 14,304 exerted a minor influence on the bronchial smooth muscle tone per se or on contractions evoked by acetylcholine or neurokinin A. This suggested that the inhibitory responses were caused by a prejunctional action reducing the release of transmitter substances from sensory and cholinergic nerve endings. Furthermore NPY (10(-7) M) seemed to be more potent to inhibit both contractile components than noradrenaline (10(-6) M) in the presence of propranolol (3 X 10(-6) M). Morphine was able to reduce the e-NANC response via a naloxone-sensitive mechanism. The capsaicin-evoked bronchoconstriction and the bronchodilator NANC effect evoked by field stimulation were, however, not influenced by UK 14,304. It is concluded that NPY, alpha 2-receptor and opiate receptor activation inhibit the release of sensory transmitters evoked by field stimulation but not by capsaicin.

Animals↗
PubMed1989

Vagal vasodilatory mechanisms in the pig bronchial circulation preferentially involves sensory nerves.

The present study shows that in contrast to the upper trachea, where the parasympathetic vasodilatory components of both cholinergic and non-cholinergic nature are dominating, the vagal blood flow regulation in the peripheral airways of the pig supplied by the bronchial artery is entirely carried out by local release of vasodilatory mediators from capsaicin-sensitive sensory nerves. Also inhalation of the vapour phase from the major airway irritant cigarette smoke was associated with a marked increase in bronchial blood flow possibly via local axon reflexes. Capsaicin, substance P (SP) and calcitonin gene-related peptide (CGRP) caused vasodilatation in both the trachea and bronchi while vasoactive intestinal polypeptide (VIP) was most active in the trachea. These functional data were supported by immunohistochemical studies showing the presence of SP- and CGRP-containing nerves of presumably sensory origin around bronchial blood vessels while VIP-positive perivascular fibres of local parasympathetic origin were found mainly in the trachea.

Animals↗
PubMed1989

Effect of endothelin-1 on regional vascular resistances in the pig.

The actions of endothelin-1 (ET-1) on vascular resistances were investigated and characterized in anesthetized pigs in vivo. Intravenously administered ET-1 (2-400 pmol/kg) caused dose-dependent increases in mean arterial blood pressure accompanied by a reduction in heart rate. ET-1 also increased renal, coronary, femoral, and bronchial vascular resistances. The kidney was about 10 times more sensitive to ET-1 than the other regions. The ET-1-induced vasoconstriction in the kidney was attenuated by nifedipine (100 micrograms/kg). The responses to ET-1 in the femoral and bronchial vascular beds were biphasic with an initial decrease followed by an increase in vascular resistance at high doses. It is concluded that ET-1 causes dose-dependent vasoconstriction in several vascular beds in vivo with the most pronounced effects in the renal circulation.

Animals↗
PubMed1989

In vitro desensitization of beta-adrenoceptors in guinea pig trachea: interactions between beta-adrenoceptor agonists and influence of adenosine and other drugs.

The aim of this study was to investigate quantitatively the action of and the interaction between beta-adrenergic receptor agonists in desensitizing guinea pig isolated trachea. It was also to evaluate the influence of substances whose effects on desensitization are either disputed (theophylline, indomethacin, ketotifen, hydrocortisone) or unknown (nicardipine, Bay K 8644, fenspiride, adenosine). Tracheal strips were contracted with histamine (5 x 10(-5) M) or acetylcholine (5.10(-5) M) and concentration-response (C/R) curves for various beta-adrenoceptor agonists were determined before and after incubation (20 min to 4 h) with the same beta-adrenoceptor agonist (autodesensitization), with other beta-adrenoceptor agonists (cross-desensitization), or with a beta-adrenoceptor agonist and another substance. Our results show that the autodesensitization induced by isoprenaline is concentration dependent and that concentration dependence is more pronounced with salbutamol and fenoterol than with isoprenaline and adrenaline with respect to autodesensitization: shifts (log unit) of the C/R curves were 0.59 +/- 0.06 (N = 5) for salbutamol (10(-5) M), 0.78 +/- 0.09 (N = 5) for fenoterol (10(-6) M), 0.30 +/- 0.04 (N = 9) for isoprenaline (10(-5) M), and 0.33 +/- 0.05 (N = 5) for adrenaline (10(-5) M). Our studies of cross-desensitization (desensitization to isoprenaline, adrenaline, salbutamol, and fenoterol induced by incubation with isoprenaline 10(-5) M) showed a significantly greater shift in the C/R curves for fenoterol (0.56 +/- 0.08, N = 5) and salbutamol (0.62 +/- 0.05, N = 5) than for adrenaline (0.35 +/- 0.07, N = 5) and isoprenaline itself (0.30 +/- 0.05, N = 9). Of the substances we studied, none modified the desensitization induced by isoprenaline except hydrocortisone and adenosine. Hydrocortisone (10(-8) M) reduced it significantly, although to a negligible extent. Adenosine (3 x 10(-4) M) did not shift the C/R curve to isoprenaline by itself, but incubation of tracheal strips with adenosine and isoprenaline caused a significantly greater shift of C/R curves to isoprenaline (0.30 +/- 0.04) than incubation with isoprenaline alone (0.20 +/- 0.04) (P less than 0.05, N = 5). These experiments suggest that adenosine may have increased the uncoupling and/or down-regulation phenomena induced by isoprenaline, or modified adenylate cyclase-cAMP activity.

Adenosine↗
PubMed1989

Effects of neuropeptides and capsaicin on tracheobronchial blood flow of the pig.

Blood flow changes upon systemic i.v. injections in the pig of various neuropeptides, capsaicin, bradykinin and histamine were directly monitored by a Transonic blood flowmeter in the superior laryngeal, bronchial and femoral arteries and indirectly in the larynx and skin using laser Doppler flowmetry. To minimize influence of compensatory reflexes and indirect effects, the pigs were pre-treated with atropine, guanethidine, chlorisondamine and capsaicin. Substance P (SP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), calcitonin gene-related peptide (CGRP), capsaicin, bradykinin and histamine all decreased vascular resistance, suggesting vasodilation in the superior laryngeal and bronchial arteries. All peptides and histamine when given i.v. exerted vasodilatory effects independent of autonomic motor nerves and capsaicin-sensitive afferents. SP was the most potent vasodilator agent tested in both tracheal and bronchial circulation, being about 1000-fold more active than histamine. VIP was about 10-fold more potent than PHI in decreasing vascular resistance and had a preferential action on the SLA compared to CGRP. In the femoral artery capsaicin and also SP in the highest dose increased vascular resistance. Capsaicin increased the laser Doppler signal in both laryngeal mucosa and skin, while i.v. peptides caused variable effects. In conclusion, SP and CGRP mimicked capsaicin-induced vasodilation in the tracheobronchial circulation while VIP had a preferential effect on the tracheal circulation.

Animals↗
PubMed1989

Vagally mediated vasodilatation by motor and sensory nerves in the tracheal and bronchial circulation of the pig.

A new in vivo model is described in which anaesthetized pigs were used to study vascular responses in the bronchial, upper tracheal and laryngeal circulation upon electrical stimulation of the vagal or superior laryngeal nerves. Vagal or superior laryngeal nerve stimulation increased blood flow in the bronchial artery and the superior laryngeal artery, respectively. After pre-treatment with atropine the vasodilatory response in the bronchial artery upon stimulation was not modified while the increase in blood flow in the superior laryngeal artery was reduced. The ganglionic blocking agent chlorisondamine further reduced the nerve stimulation evoked decrease in vascular resistance in the superior laryngeal artery, but did not influence the response of the bronchial artery. Capsaicin induced a marked increase in blood flow both in the bronchial and superior laryngeal arteries after pre-treatment with atropine, guanethidine and chlorisondamine. After capsaicin tachyphylaxis, the vasodilatation upon nerve stimulation in the bronchial artery and the smaller remaining decrease in vascular resistance in the superior laryngeal artery were strongly reduced. Thus, antidromic stimulation of afferent C fibres may increase blood flow via release of vasodilatory peptides such as tachykinins and calcitonin gene-related peptide. The present findings show that local blood flow in the larynx and upper trachea is regulated by cholinergic and non-cholinergic parasympathetic mechanisms and a small capsaicin sensitive, sensory component. On the other hand, the vagal control of the bronchial circulation seems to exclusively involve capsaicin sensitive sensory nerves.

Animals↗
PubMed1988

Interaction between fenoterol, ipratropium, and acetylcholine on human isolated bronchus.

Functional antagonism between fenoterol (F) and acetylcholine (ACh) and interaction between F and ipratropium (Ipr) on ACh-induced contraction were evaluated on isolated human bronchi. In the presence of increasing concentrations of ACh (2 X 10(-4) and 2 X 10(-3) mol/L), dose-response curves of the relaxant effect of F were shifted to the right (0.45 and 0.92 log units), and the maximal effect of F, expressed as a percentage of the effect of theophylline, 3 X 10(-3) mol/L, was reduced from control values of 92.1 +/- 4% to 70.8 +/- 7.0%, and to 67.2 +/- 7.1%, according to the functional antagonism. In the presence of Ipr, 10(-9) and 10(-8) mol/L, the functional antagonism between ACh and F was partially reversed. Concentration response-curves to F versus ACh, 2 X 10(-3) mol/L, were shifted to the left, and although the -log molar concentration producing 50% of maximal effect was not significantly modified, the maximal effect of F was significantly increased in the presence of Ipr, 10(-8) mol/L. It is concluded that the effect of combined F and Ipr on the isolated human bronchus contracted with ACh appears to be of the additive type.

Acetylcholine↗
PubMed1988

Comparative effects of rilmenidine and clonidine on bronchial responses to histamine in asthmatic subjects.

1. The effects of pretreatment with clonidine and rilmenidine, a new alpha 2-adrenoceptor agonist, on the bronchial responses to inhaled histamine were studied on 3 different days in a controlled, double-blind, randomized study in 12 asymptomatic asthmatic subjects. Clonidine and rilmenidine were orally administered as single and equipotent doses of 150 micrograms and 1 mg, respectively. All the subjects were non-smokers with normal lung function tests (forced expiratory volume in one second (FEV1) = 97 +/- 10% predicted FEV1). 2. Histamine (first dose = 543 nmol) was delivered by a breath activated dosimeter (DeVilbiss no. 646 nebulizer) every 5 min; FEV1 was measured in triplicate after each dose and the largest value was analyse. The three dose-response curves were compared by analysis of variance. 3. Both clonidine and rilmenidine decreased arterial blood pressure in all subjects. There was no difference in baseline values and pre-challenge values of FEV1 after placebo, clonidine and rilmenidine on the 3 study days. Compared with placebo, both rilmenidine and clonidine significantly increased the bronchial responses to histamine (P less than 0.05 and P less than 0.01 respectively) an effect which was significantly more marked with clonidine than rilmenidine (P less than 0.05). 4. We suggest that the enhancement of bronchial responsiveness to histamine by clonidine and rilmenidine may result from their effects on both central and peripheral alpha 2-adrenoceptors, and that the lesser aggravation of histamine-induced bronchial obstruction in asthmatic subjects on rilmenidine might be explained by its lesser central and/or greater peripheral effects than clonidine.

Adrenergic alpha-Agonists↗
PubMed1988

Role of extracellular calcium in the effects of substance P and neurokinin A on guinea pig trachea and human bronchus.

Whether the influx of calcium through voltage-operated channels is involved in the stimulatory effects of substance P and neurokinin A in airways smooth muscle is not yet firmly established. This question was addressed in the present study using guinea pig trachea and human bronchi suspended in normal or calcium-free Krebs solution and tested with inhibitors of calcium channels. In calcium-free Krebs solution, the myotropic effects of substance P (10(-7) M), neurokinin A (3.10(-8) M), acetylcholine (2.10(-5) M), and histamine (2.10(-5) M) were reduced by 27-57%, while those of potassium chloride and tetraethylammonium were practically abolished. Calcium antagonists such as verapamil or nicardipine, when applied at concentrations of 10(-8)-10(-6) M, inhibited the contractions produced by potassium chloride and tetraethylammonium, whereas higher concentrations (10(-5)-10(-4) M) of both inhibitors were needed to reduce the effects of substance P, neurokinin A, acetylcholine, and histamine. In neither preparation did the calcium agonist Bay K 8644 (10(-6) M) modify the effects of neurokinin A, substance P, acetylcholine, or histamine, but it potentiated potassium chloride's effect on human bronchi. We conclude that transmembrane calcium influx through voltage-operated channels plays a minor role in the stimulatory effects of neurokinins in airways smooth muscle.

Animals↗
PubMed1988

Effects of noradrenaline on the isolated human bronchus. Comparison with the isolated guinea pig trachea.

The pharmacodynamic activity of noradrenaline was evaluated comparatively in vitro on isolated human bronchi and on guinea pig tracheal spirals. Noradrenaline exerted a contractile effect on both preparations under resting tone and in the presence of propranolol 10(-6) M; maximal noradrenaline-induced contraction was 15-20% of maximal acetylcholine (ACh)-induced contraction. Without propranolol, the contractile effect of noradrenaline was negligible when the preparations were under resting tone and absent when they were precontracted with ACh. In contrast, noradrenaline exerted a strongly relaxant effect on both human bronchi (-log ED50 5.24 +/- 0.17; N = 5) and guinea pig tracheae (-log ED50 6.15 +/- 0.29; N = 8). With maximal contraction induced by ACh 3.10(-3) M the -log ED50 of both preparations were shifted to the right by functional antagonism and became 4.72 +/- 0.17 and 5.31 +/- 0.11, respectively. The pKD values of noradrenaline, calculated according to Furchgott and Bursztyn (1967), were 4.79 +/- 0.04 in human bronchi (N = 5) and 4.77 +/- 0.16 in guinea-pig tracheae (N = 8). In the presence of cocaine plus phenoxybenzamine these values were not significantly modified in human bronchi and only slightly modified in guinea pig tracheae. It is concluded that noradrenaline induces a strong beta-adrenergic response and a negligible alpha-adrenergic response from both human bronchi and guinea pig tracheae in vitro.

Animals↗
PubMed1988

Influence of epithelium on the responsiveness of guinea-pig isolated trachea to adenosine.

1. The influence of epithelium removal on the effects of adenosine on airway contractility was investigated on the guinea-pig isolated trachea. 2. In preparations under resting tone or precontracted with histamine 10(-5) M, removal of the tracheal epithelium resulted in similar shifts to the left of the adenosine concentration-response curves (0.61 +/- 0.18 (P less than 0.05) and 0.80 +/- 0.09 (P less than 0.001) log units; n = 5), corresponding to 4.07 and 6.31 fold potentiations of the relaxant effect of adenosine. 3. In the presence of dipyridamole 10(-5) M the relaxant effects of adenosine were potentiated 85.1 fold on tracheae with epithelium; removal of the epithelium did not produce a significant additional shift to the left of the adenosine concentration-response curves (0.07 +/- 0.03 log units; n = 5; NS). 4. In the absence of dipyridamole, the theophylline-adenosine antagonism was not of the competitive type, irrespective of whether the tracheae were with or without epithelium. 5. In the presence of dipyridamole, this antagonism was likely to be of the competitive type and its characteristics were the same when the epithelium was present or absent. Regression slope and pA2 values were 0.84 and 5.07, respectively, in the presence of epithelium and 0.76 and 4.89, respectively, in its absence. 6. It is suggested that, at least in the guinea-pig isolated trachea model, the airway epithelium seems to be involved only in the uptake and metabolism of adenosine.

Adenosine↗