Increased Tracheal Responsiveness to Beta-Adrenergic Agonist and Antagonist in Ovalbumin-Sensitized Guinea Pigs

Abstract

Despite the controversy of bronchial responsiveness to β₂-agonist drugs in asthma, in a previous study we have shown increased responsiveness of asthmatic tracheobronchial tree to isoprenaline. Therefore, in the present study, tracheal responsiveness to isoprenaline and also β-adrenergic receptor blockade were studied in sensitized guinea pigs. An experimental model of asthma was induced in guinea pigs by sensitization of animals with injection and inhalation of ovalbumin (OA). The responses of tracheal chains of sensitized and control animals to cumulative concentrations of isoprenaline (I) in the absence and presence of 10 nmol/l propranolol were measured, and the effective concentration of I causing 50% of maximum response (EC₅₀ I) was obtained. The propranolol blockade (CR – 1) was calculated by: (post-propranolol EC₅₀ I/EC₅₀ I) – 1. Tracheal responses of sensitized and control animals to cumulative concentrations of methacholine (M) were also measured and EC₅₀ M were obtained. The tracheal responses of sensitized guinea pig to isoprenaline was significantly higher than that of the control animals (EC₅₀ I for sensitized and control animals were 0.24 ± 0.04 and 0.58 ± 0.07 µmol/l, respectively; p < 0.001).The β-adrenergic receptor blockade by propranolol (CR – 1) was also significantly higher in sensitized guinea pigs than that of the control animals (p < 0.001). The results of this study indicate an increased tracheal response to β-adrenergic-stimulating drug and enhancement of β-adrenergic blockade by propranolol in the sensitized guinea pig.

Tracheal responsiveness to both isoprenaline and beta2‐adrenoreceptor blockade by propranolol in cigarette smoke exposed and sensitized guinea pigs

“…The histological findings in AECS showed increased interalveolar septum and lymphatic tissue, destruction of alveolar walls and intra‐alveolar bleeding as was to that observed in previous studies 5,25 , 26 . The increased tracheal response to isoprenaline in AECS + sensitized confirmed the induction of experimental asthma and the tracheal responsiveness to a β‐agonist drug was similar to our previous studies 15–18 …”

“…The increased propranolol blockade in tracheal chains of AECS and AECS + sensitized guinea pigs, as well as the increased chlorpheniramine, atropine, and propranolol blockade in our previous in vivo studies in asthmatic patients 15,42 , 44 and enhanced atropine, chlorpheniramine and propranolol blockade in tracheal chains of sensitized animal studies, 16,27 , 28 could be due to higher concentration of antagonists at the receptor sites achieved by an increased epithelial and tissue permeability leading to an increase in [I]. Destruction of lung parenchyma has been documented in AECS 21 and thus, increased tissue permeability and better accessibility of ligands to the receptor sites is possible.…”

“…5,25,26 The increased tracheal response to isoprenaline in AECS + sensitized confirmed the induction of experimental asthma and the tracheal responsiveness to a β-agonist drug was similar to our previous studies. [15][16][17][18] Several other studies have shown AHR to different stimuli in guinea pig exposed to cigarette smoke. [6][7][8][9][10] However, the present study demonstrated an increased tracheal responsiveness to isoprenaline and β-adrenergic receptor blockade by propranolol (CR-1) in both AECS and AECS + sensitized.…”

“…Previous studies have shown very similar dose-response relationships to β-agonists in normal and asthmatic subjects. [11][12][13][14] Our previous studies showed an increased bronchial responsiveness to isoprenaline in asthmatics compared with normal subjects, 15 in sensitized compared with control animals 16 and in epithelium denuded trachea compared with intact epithelium trachea. 17 In addition, in recent studies, increased airway responsiveness to salbutamol in smokers compared with non-smoking subjects and asthmatics has been demonstrated.…”

Pharmacologic bronchodilation response to salbutamol in copd patients

“…[12] This hypothesis was then tested with another β-agonist (salbutamol) in asthmatic patients and also in smokers. [13,14] This phenomenon was also demonstrated in tracheal chains of sensitized and COPD animals [30,31] as well as epithelial denuded trachea. [32] In most of the above-mentioned studies a close correlation was found between airway responsiveness to methacholine and β-agonist.…”