Thromboxane A2 biosynthesis in acute asthma and after antigen challenge.
Thromboxane A2 is a potent bronchial smooth muscle spasmogen in vitro, and it has been implicated in airway inflammation and in the genesis of bronchial hyperresponsiveness in asthma. We have examined the urinary excretion of a variety of products derived from thromboxane A2 (thromboxane B2, 2,3-dinor, and 11-dehydro-thromboxane B2) and prostacyclin (6-oxo-PGF1 alpha and 2,3-dinor-6-oxo-PGF1 alpha) using gas chromatography-mass spectrometry in patients admitted acutely to hospital with severe asthma and in atopic volunteers after bronchial antigen challenge. Urinary excretion of all thromboxane-derived products was markedly increased in a number of patients with severe acute asthma compared with that in a nonsmoking control population, in some cases approaching those previously described in myocardial infarction: TXB2, 31.6 +/- 12.0 versus 6.5 +/- 0.9; 2,3-dinor-TXB2, 79.0 +/- 19.2 versus 29.5 +/- 2.7; and 11-dehydro-TXB2, 234.3 +/- 65.3 versus 25.0 +/- 2.1 ng/mmol creatinine (p less than 0.001). Urinary prostacyclin-derived products were also significantly raised in acute asthma. In contrast, after inhaled allergen challenge in atopic volunteers, which caused significant bronchoconstriction, urinary excretion of thromboxane-derived products was not significantly elevated: TXB2, 5.6 +/- 1.1 versus 5.7 +/- 1.0; 2,3-dinor-TXB2, 41.2 +/- 12.5 versus 28.5 +/- 6.9; and 11-dehydro-TXB2, 69.8 +/- 17.6 versus 39.7 +/- 11.2 ng/mmol creatinine. In a separate experiment, less than 2% of exogenously administered TXB2 to the airway appeared as urinary thromboxane-derived products, suggesting that production of greater than or equal to 1 microgram of TXA2 in vivo would be required to increase urinary thromboxane excretion twofold.(ABSTRACT TRUNCATED AT 250 WORDS)
Taylor
I K
IK
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, United Kingdom.
Ward
P S
PS
O'Shaughnessy
K M
KM
Dollery
C T
CT
Black
P
P
Barrow
S E
SE
Taylor
G W
GW
Fuller
R W
RW
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000485:Allergens; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine; D001985:Bronchial Provocation Tests; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000652:urine; D013928:Thromboxane A2 / Q000008:administration & dosage / Q000096:biosynthesis* / Q000652:urine
D000485:Allergens; D011453:Prostaglandins; D013928:Thromboxane A2