Réactivité bronchique du cobaye et système adrénergique

La mécanique ventilatoire, par la mesure des variations de la pression transpulmonaire, est appliquée aux cobayes normaux et sensibilisés afin d'apprécier l'effet de l'inhalation de divers agents bronchomoteurs.

Seule une proportion modérée de cobayes non sensibilisés développe d'emblée un bronchospasme sous l'action de l'histamine, de l'acétylcholine, de la 5 HT et de la bradykinine. Les processus actifs de sensibilisation allergique intensifient la réactivité bronchique des cobayes à l'égard des agents pharmacodynamiques spasmogènes et démasquent l'effet bronchoconstricteur de la noradrénaline.

Le blocage des β-récepteurs adrénergiques locaux par l'aérosol de propranolol exalte chez les cobayes, tant normaux que sensibilisés, la réactivité bronchique pharmacodynamique tandis qu'il fait apparaître ou qu'il intensifie la réponse bronchospastique de ces animaux à l'aérosol de noradrénaline.

De plus, chez les cobayes sensibilisés, le propranolol accroît la bronchoconstrirtion anaphylactique ou s'avère capable soit de démasquer le spasme résultant de l'inhalation de l'allergène soit de régénérer l'action bronchospastique de cette dernière préalablement épuisée par anti-anaphylaxie.

La réactivité bronchique du cobaye est donc soumise à l'activité du système adrénergique. L'activité des β-récepteurs normalement prépondérante au niveau des bronches, entretient un tonus bronchodilatateur qui s'oppose à l'action spastique des divers agents bronchomoteurs. L'inhibition de ces récepteurs soit spontanée, soit pharmacodynamique, soit secondaire au développement de processus allergiques, fait naître un état d'hyperexcitabilité de la musculature bronchique. Dans ces conditions, l'action motrice des récepteurs α-adrénergiques peut être démasquée et l'excitation de ces récepteurs engendre un bronchospasme qu'inhibent les adrénolytiques de type α.

Le cobaye s'avère donc un modèle de la réactivité bronchique de l'homme normal et bronchospastique.

Bronchial reaction in guinea-pigs of the Hartley strain was studied by simultaneous recording of output variations, pulmonary volume and transpulmonary pressure when the air supply was repeatedly cut off. This method enabled quantitative measurements to be made of changes in compliance and dynamic resistance of the lungs. It also allowed an assessment to be made of the ventilatory asynchronism present in all bronchospastic reactions.

A small proportion only of our un-sensitized guinea-pigs showed spontaneous bronchospasm under the influence of aerosols obtained from reputedly broncho-constricting pharmacodynamic agents : histamine, 5 HT, bradykinin, acetylcholine. Frequently, in fact, aerosols of these substances proved either inactive or caused a sudden isolated drop in pulmonary compliance which, in the absence of appreciable changes in the dynamic resistance of the lungs, cannot be attributed to a loss of bronchial permeability.

Following allergic sensitization procedures and under the influence of propranolol induced inhibitory action on the part of the β adrenergic receptors, the number of guinea-pigs exhibiting bronchospasm after inhalation of the same bronchomotor agents rises significantly. At the same time, a bronchospastic effect occurs when noradrenaline is inhaled.

On the other hand, sensitization produces a marked potentiation of pre-existing bronchial reactivity similar to that produced by inhalation of propranolol.

This substance also proved to be a powerful potentiator of anaphylactic responses and enabled these to be detected in slightly sensitized guinea-pigs which were otherwise insensitive to the bronchomotor effect of the causative allergen. In addition, a single administration of propranolol aerosol may the appearance of a bronchospasm resulting from stimulation of the α adrenergic motor system by endogenous catecholamines. Inversely, adrenolytics of the α type, such as phentolamine and thymoxamine, clearly play a protective role in bronchospasm of anaphylactic or pharmacodynamic origin. These experimental findings confirm that bronchial reaction in guinea-pigs is controlled by the adrenergic system. The β receptors of this system, stimulated by endogenous catecholamines, maintain a bronchodilator tonus which, under normal conditions, provides effective opposition to various bronchospasmogenic stimuli.

Inadequate tonicity, caused by spontaneous or induced inhibition of the β adrenergic receptors, controls the degree of bronchial reactivity to the various exogenous and endogenous pharmacodynamic bronchoconstrictor agents liberated by the anaphylactic processes.

Finally, β receptor blocking shows up the role of α adrenergic broncho-constriction caused by endogenous and exogenous noradrenaline. That is why α adrenergic receptors play a part in various bronchomotor responses. The obvious inhibitory effect of α type adrenolytics on bronchospasm of a pharmacodynamic or allergic nature is proof of this function. Bronchospasmolytic activity of the adrenolytics results from suppression of the particular bronchomotor effect of the α adrenergic receptors. It may also result from a decrease in the quantity of chemical mediators liberated at the time of the allergic reaction and from protection of cyclic AMP reserves. Similar regulation of bronchial reaction via the adrenergic system is found in humans under the same experimental or physiopathological conditions, a similarity which justifies this important piece of research carried out into bronchomotricity in guinea-pigs.