The effect of inhaled 15-(s)-hydroxyeicosatetraenoic acid (15-HETE) on airway calibre and non-specific responsiveness in normal and asthmatic human subjects

Abstract

15-hydroxyeicosatetraenoic acid (15-HETE) is the predominant oxidative metabolite of arachidonic acid in human lung. We have studied its effects on airway calibre and non-specific bronchial responsiveness (NSBR) in eight normal and eight asthmatic subjects. 15-HETE, at doses up to 70 nmol, had no effect on airway calibre in either group of subjects. However, 3 h after its administration, 15-HETE reduced NSBR in the normal subjects (geometric mean methacholine PD40 V̇p30 increased by 2.29-fold from baseline compared with a corresponding 1.14-fold increase after diluent, p<0.05). Similarly, 4 h after inhaled 15-HETE, the spontaneous increase in NSBR in the asthmatics was completely inhibited (geometric mean histamine PD40 V̇p30 decreased significantly to 0.41-fold of baseline after diluent (p<0.01) compared with a 1.1-fold increase after 15-HETE, p<0.01). These data suggest 15-HETE may play an autacoid role in airway function.