COMPARISON OF THE EFFECTS OF SALBUTAMOL AND ADRENALINE ON AIRWAY SMOOTH-MUSCLE CONTRACTILITY IN-VITRO AND ON BRONCHIAL REACTIVITY IN-VIVO

Background - The effect of adrenergic agonists in asthma depends on th eir net effect on microvascular leakage, mucosal oedema, vascular clea rance of spasmogens, inhibition of cholinergic neurotransmission, and airway smooth muscle contractility. It has been postulated that adrena line, by virtue of its alpha effects on the vasculature and cholinergi c neurotransmission, may have additional useful properties in asthma c ompared with selective beta agonists such as salbutamol. Methods - The airway effects of adrenaline (a non-selective adrenoreceptor agonist) were compared with the selective beta(2) agonist salbutamol. Their ai rway smooth muscle relaxant potencies and effect on histamine contract ion in human bronchi in vitro were compared with their effects on airw ay calibre and histamine reactivity in asthmatic subjects in vivo. For the in vitro studies changes in tension were measured in response to these agents in thoracotomy specimens of human airways. In vivo the ef fects of adrenaline and salbutamol on airway calibre and histamine rea ctivity were measured in eight subjects with mild to moderate asthma i n a randomised crossover study. Results - Salbutamol and adrenaline ha d approximately equivalent airway smooth muscle relaxant potencies in vitro and bronchodilator potency in vivo. However, their effects on hi stamine induced contraction in vitro were significantly different from their effects on histamine reactivity in vivo. Salbutamol was less po tent in vitro producing a mean (SE) 2.4 (0.15) doubling dose increase in the histamine EC(50) and adrenaline a 5.2 (0.18) doubling dose incr ease (mean difference between salbutamol and adrenaline 2.8 doubling d oses; 95% CI 1.1 to 4.5). Salbutamol had no effect on the maximal resp onse to histamine whereas adrenaline reduced it by 54%. In contrast, s albutamol was more potent in vivo producing a mean (SE) increase in PD 20 histamine of 1.84 (0.5) doubling doses whereas adrenaline was witho ut effect increasing PD20 by only 0.06 (0.47) doubling doses (mean dif ference between adrenaline and salbutamol 1.78, 95% CI 0.26 to 3.29 do ubling doses). Conclusions - These findings suggest that the alpha adr energic airway effects of nonselective adrenoreceptor agonists such as adrenaline offer no additional protection against histamine-induced b ronchoconstriction in vivo than beta(2) selective drugs such as salbut amol, despite adrenaline providing greater protection against histamin e-induced contraction in vitro, The differences between the effects of these agents in vitro and in vivo may be related to their opposing va scular effects in vivo.