The effect of inhaled 15-(s)-hydroxyeicosatetraenoic acid (15-HETE) on airway calibre and non-specific responsiveness in normal and asthmatic human subjects.
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 Vp30 increased by 2.29-fold from baseline compared with a corresponding 1.14-fold increase after diluent, p less than 0.05). Similarly, 4 h after inhaled 15-HETE, the spontaneous increase in NSBR in the asthmatics was completely inhibited (geometric mean histamine PD40 Vp30 decreased significantly to 0.41-fold of baseline after diluent (p less than 0.01) compared with a 1.1-fold increase after 15-HETE, p less than 0.01). These data suggest 15-HETE may play an autacoid role in airway function.
Lai
C K
CK
Immunopharmacology Group, Southampton General Hospital, UK.
Phillips
G D
GD
Jenkins
J R
JR
Holgate
S T
ST
D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects; D001985:Bronchial Provocation Tests; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D012107:Research Design; D013997:Time Factors
D006893:Hydroxyeicosatetraenoic Acids; D008688:Methacholine Compounds; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D006632:Histamine