Influence of circulating alpha adrenoceptor agonists on lung function in patients with exercise induced asthma and healthy subjects.

Abstract

The influence of circulating noradrenaline (in this context primarily a non-selective ai agonist) and the a, selective agonist phenylephrine on bronchial tone, blood pressure, and heart rate was studied in eight patients with exercise induced asthma and eight age and sex matched controls. All subjects refrained from taking treatment for at least one week before the trial. The agonists were infused intravenously in stepwise increasing doses of 0.04, 0.085, 0.17, and 0.34 Mg/kg a minute for noradrenaline and 0.5, 1.0, 2.0, and 4.0 Mg/kg a minute for phenylephrine. At the highest dose the plasma concentration of noradrenaline was about 30 nmol/l, resembling the concentrations found during intense exercise, and that of phenylephrine was about 400 nmol/l. Both agonists caused dose dependent and similar increases in blood pressure in the two groups. Despite clearcut cardiovascular effects (systolic and diastolic blood pressure increased by about 40-50/25-30mm Hg), neither agonist altered lung function, as assessed by measurements of specific airway compliance (sGaw), peak expiratory flow (PEF), or end expiratory flow rate, in either group. It is concluded that circulating oc agonists, whether a, selective (phenylephrine) or non-selective (noradrenaline), fail to alter basal bronchial tone in patients with exercise induced asthma or in healthy subjects.The role of pulmonary a adrenoceptors in asthma is not clear. Inhaled a agonists have usually caused bronchoconstriction in asthmatic patients but not in healthy subjects,'`3 though a small but significant effect has been shown in some healthy subjects.4 These in vivo findings are consistent with some in vitro findings that suggest the presence of a adrenoceptor mediated constriction of human airways smooth muscle. Whether or not the a adrenoceptor sensitivity of asthmatic patients is different from that of controls is also debated. One study has shown greater a adrenoceptor mediated vascular and pupillary smooth muscle responses in asthmatic patients than in healthy controls.'5 Another study, however, showed that the a2 adrenergic responses of platelets were similar in asthmatic and in healthy subjects.16The aim of the present study was to investigate pulmonary and cardiovascular responses to circulating a adrenoceptor agonists in asthmatic patients. We studied the effect of intravenous phenylephrine (an a, selective agonist) and noradrenaline on the airways, blood pressures, and heart rates of patients with exercise induced asthma and matched healthy controls. Circulating noradrenaline acts mainly as a nonselective7 a adrenoceptor agonist, as indicated by a lack of effect of P blockade on blood pressure and heart rate responses to infused noradrenaline in man.'8 Noradrenaline has fi, stimulating properties, but this does not cause bronchodilatation in man.l9 The effects of Pi selective and non-selective I blockade on responses to infused noradrenaline are very 552 on 11 May 2018 by guest. Protected by copyright.

Posture-induced airflow limitation in asthma: relationship to plasma catecholamines and an inhaled anticholinergic agent

“…Since circulating noradrenaline does not influence bronchial tone or reactivity [19,20), the effects of circulating catecholamines on the airways are caused by adrenaline. There is no circadian variation in the response to B-adrenoceptor stimulation [21], but it has been found that the morning-dip in lung function c oincides with trough values in plasma adrenaline levels and a causal connection between these two phenomena has been proposed [2,3).…”