Group B streptococcus promotes oxygen radical-dependent thromboxane accumulation in young piglets.
Both thromboxane A2 and oxygen-derived free radicals appear to play central roles in group B streptococcus (GBS)-induced pulmonary hypertension in piglets. This study tested the hypothesis that GBS promotes oxygen radical-dependent thromboxane accumulation and pulmonary hypertension in infant piglets. Piglets 4-12 d old were anesthetized and prepared for assessment of pulmonary arterial pressure and arterial blood gases. In control animals, GBS (10(8) organisms/kg/min for 15 min) increased mean pulmonary artery pressure by 30 +/- 1.5 torr and reduced arterial PO2 by 100 +/- 20 torr. Thromboxane A2, radioimmunoassayed in venous blood as thromboxane B2, increased by 2452 +/- 800 pg/mL. A second group of piglets was treated with dimethylthiourea (DMTU: 750 mg/kg), a putative oxygen radical scavenger. In these animals, GBS increased pulmonary arterial pressure by only 7 +/- 1 torr and reduced arterial PO2 by a modest 10 +/- 8 torr. Importantly, thromboxane B2 content in venous blood failed to increase above control levels in DMTU-treated animals. The protective effects of DMTU in GBS-treated piglets could not be ascribed to inhibition of cyclooxygenase or thromboxane synthase because the oxygen radical scavenger failed to attenuate increases in pulmonary arterial pressure and venous thromboxane B2 content or reductions in arterial PO2 caused by i.v. infusions of arachidonic acid. DMTU also did not ameliorate pulmonary hypertension evoked by the thromboxane mimetic U44069, thereby suggesting that the scavenger did not act as an end-organ antagonist of thromboxane receptors. These observations suggest that GBS promotes accumulation of thromboxane A2 and attendant pulmonary hypertension through an oxygen radical-dependent mechanism.
Shook
L A
LA
University of Kentucky A.B. Chandler Medical Center, College of Medicine, Department of Pediatrics, Lexington.
Pauly
T H
TH
Marple
S L
SL
Horstman
S J
SJ
Tai
H H
HH
Bowdy
B D
BD
Gillespie
M N
MN
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D005609:Free Radicals; D006976:Hypertension, Pulmonary / Q000209:etiology; D010100:Oxygen / Q000097:blood*; D013290:Streptococcal Infections / Q000097:blood* / Q000150:complications; D013292:Streptococcus agalactiae; D013552:Swine; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood*
D001095:Arachidonic Acids; D005609:Free Radicals; D016718:Arachidonic Acid; D013929:Thromboxane B2; C038983:1,3-dimethylthiourea; D013890:Thiourea; D010100:Oxygen