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Biomedical subjects

C Brink

Publications and source records attributed to C Brink.

At least 91 records · Page 5Linked to original sources
PubMed1982

Beta-receptors during aging in respiratory tissues.

Specific [125I] hydroxybenzylpindolol binding (33 fmol/mg protein) was detected in tracheal tissues from middle aged (417 g) and old (757 g) guinea pigs but binding was not measurable in tracheal tissues from young (118 g) animals. Similarly, receptor density increased in bronchial and parenchymal tissues during development but receptor affinity did not change. For any age, the receptor densities were parenchyma greater than bronchi greater than trachea (20/7/1); receptor affinities were identical. The potency of l-isoproterenol in relaxing bronchial muscle was reduced during development. In vivo, salbutamol reduced airway reactivity to histamine and was most potent in animals exhibiting airway hyperreactivity. In addition, l-propranolol sensitized airway muscle to the bronchoconstrictor effects of histamine in young guinea pigs; in old guinea pigs of the same airway reactivity, l-propranolol did not affect the induced bronchoconstriction. Our data suggest that there is a reduced sensitivity of airway muscle to catecholamines during development which may be due, in part, to increased density of beta-adrenoceptors which are not involved in eliciting the physiological response.

Aging↗
PubMed1982

Changes in the response of guinea-pig airways in vivo and in vitro to cimetidine and propranolol during development.

1 Airway responses were examined in isolated tissues and in whole animal preparation of female albino guinea-pigs of known age. 2 Tone induced with acetylcholine in tracheal and bronchial tissues from young and old female guinea-pigs was not reduced by dimaprit or 4-methyl histamine even in tissues pretreated with mepyramine maleate. 3 Antagonism of H2-receptors with cimetidine did not affect the potency or efficacy of histamine in tracheal tissues from animals of either age group. 4 After cimetidine treatment the potency of histamine was increased in bronchial tissues from old but not young animals. The sensitizing effect was still demonstrable in tissues incubated with indomethacin. 5 In vivo airway sensitivity to threshold concentrations of histamine in animals from either age group was unaffected by cimetidine treatment. 6 Propranolol enhanced airway responses to histamine aerosols in young but not old guinea-pigs. 7 Cimetidine was without effect on histamine sensitivity in young guinea-pigs after propranolol treatment but significantly reduced airway sensitivity to histamine in old guinea-pigs. 8 Our data show that (a) H2-receptors are of no physiological significance for airway responses to histamine in vitro or in vivo and (b) during development the modulating actions of catecholamines upon airway responses are significantly reduced.

Aging↗
PubMed1981

Histamine, endogenous prostaglandins and cyclic nucleotides in the regulation of airway muscle responses in the guinea pig.

Indomethacin (30 mg/kg, i.p.) reduced pulmonary resistance in guinea pigs but did not affect their sensitivity to histamine. This treatment preferentially reduced the generation of PGE2 by isolated tracheal preparations. The ratios of PGF2 alpha/PGE2 before and after treatment were 1/1 and 6/1, respectively. Chronic indomethacin treatment (30 mg/kg, i.p., twice a day for 4 days) increased histamine sensitivity in vivo 2 fold while a longer treatment (10 days) was without effect. The efficacy of histamine and the potency of isoproterenol in tracheal tissues were unaffected by either treatment. Indomethacin (17 microM for 30 min) relaxed tracheal tissues but not bronchial tissues. Responses of both tissues to contractile agonists were potentiated after indomethacin treatment. The efficacy of histamine was smaller in bronchi than in tracheas. Similarly, PGE2, PGI2 and isoproterenol were less potent in bronchi. Basal amounts of cyclic AMP were higher in bronchi than in tracheas; indomethacin did not affect the basal amounts of cyclic AMP in tracheal tissues but reduced them in bronchial preparations. Histamine elevated cyclic AMP content in both preparations; this elevation was reduced by indomethacin. While prostaglandins play a role in modulating airway responses in vitro, their role in airways in normal animals in vivo is more difficult to demonstrate.

Airway Resistance↗
PubMed1981

Tolerance of guinea-pig airway muscle preparations to relaxant agonists induced by chronic exposure to isoprenaline in vivo.

1 The histamine sensitivities of complete tracheal spiral preparations from guinea-pigs were similar to those of paired half tracheal tissues. 2 Airway muscle preparations from animals chronically treated with isoprenaline showed a significant increase in resting tone and a significant decreased responsiveness to histamine. 3 The paired half tracheal preparations exhibited no significant difference when either their isoprenaline or theophylline sensitivities were compared. 4 Paired half tracheal muscle preparations from chronically treated animals (0.4 mumol, 4.0 mumol, and 40.0 mumol isoprenaline, 3 times daily for 21 days, s.c.) showed a significantly reduced sensitivity to isoprenaline when compared to appropriate controls. 5 Theophylline concentration-effect curves for the paired half tracheal preparations from chronically treated guinea-pigs (4.0 mumol and 40.0 mumol isoprenaline) were significantly reduced compared with appropriate controls. 5 Indomethacin treatment reversed the isoprenaline desensitization induced by chronic treatment (0.4 mumol isoprenaline) but was ineffective in animals that received the higher doses of isoprenaline in vivo.

Animals↗
PubMed1980

The interaction between indomethacin and contractile agents on human isolated airway muscle.

1 Concentration-effect curves to acetylcholine and histamine were produced in fresh human bronchial muscle (2 to 4 h after removal from the patients) and in preparations previously stored at 4 degrees C for 12 h. 2 Sensitivities of fresh human airway muscle preparations to acetylcholine (pD2 value, 5.89 +/- 0.03; n = 4) and histamine (pD2 values, 5.41 +/- 0.03; n = 13) were similar. There was no significant difference in the sensitivities of stored preparations (acetylcholine: pD2 value, 5.70 +/- 0.06; n = 23 and histamine: pD2 value, 5.44 +/- 0.07; n = 16) when compared to the fresh preparations. 3 Indomethacin did not significantly change the basal tone in preparations of either fresh or stored human airway muscle. 4 A low concentration of indomethacin (0.17 muM) significantly reduced responsiveness and sensitivity to histamine in stored bronchi but not in fresh bronchi. The acetylcholine concentration-effect curves were unaltered by exposure to this concentration of indomethacin in either fresh or stored tissues. High concentrations (1.7 muM and 17 muM) depressed the maximal responsiveness of the bronchi to both agonists. 5 These results suggest indirectly that the regulatory role of prostaglandins in human airway muscle may be different from that in other species.

Acetylcholine↗
PubMed1977

Tachyphylaxis to beta-adrenoceptor agonists in guinea pig airway smooth muscle in vivo and in vitro.

Beta-Adrenoceptor tachyphylaxis was induced by incubating spirally cut guinea pig tracheas with isoproterenol (2.4 x 10(-7) M) for 20 min. This incubation reduced the relaxant effects of catecholamines but not of dibutyryl cyclic AMP, theophylline or sodium nitrite. Tracheas incubated with norepinephrine, phosphodiesterase inhibitors or cyclic nucleotides became tachyphylactic to isoproterenol. Pretreatment with indomethacin prevented induction of tachyphylaxis. Incubation with adenosine, methoxamine or sodium nitrite did not induce beta-adrenoceptor tachyphylaxis. When we gave isoproterenol intramuscularly to guinea pigs, airway sensitivity to aerosolized histamine was unchanged but the toxicity of parenterally administered histamine was increased. A prolonged treatment with isoproterenol reduced airway sensitivity to histamine aerosols; this reduced sensitivity was reversed by indomethacin. Thus, beta-adrenoceptor tachyphylaxis may not explain increased toxicity of parenteral histamine after isoproterenol treatment. Elevated levels of cyclic AMP and an increased synthesis of prostaglandins may result in diminished response to beta-receptor stimulation.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Role of nitric oxide on cholinergic component of bronchial tone in pig.

In vitro studies demonstrated that stimulation of intrinsic nerves of airway smooth muscle results in a predominantly contractile response, followed by a relaxant response which involves cholinergic, adrenergic and non-adrenergic non-cholinergic (NANC) nerve activation. Thus, in this paper it is determined whether endogenous nitric oxide (NO) modulates cholinergic neurotransmission in isolated pig airway smooth muscle. Bronchial rings were suspended in organ baths for isometric measurement of tension and the contractions were induced using electrical field stimulation (EFS) techniques. Then, the effects of L-NG-nitroarginine (L-NOARG, 10 microM), an inhibitor of NO synthase, and L-arginine (L-ARG, 1 mM), a precursor of NO synthesis, were evaluated. The cholinergic contractions induced by electrical field stimulation (EFS: 60 V, 2 ms, 60 Hz) of pig lobar bronchial preparations increased (29%) in the presence of L-NOARG (10 microM). This effect may be released by nerves in pig large airways during EFS.

Animals↗