Role of venoconstriction in thromboxane-induced pulmonary hypertension and edema in lambs.
We evaluated the dose response to a stable thromboxane (Tx) A2 analogue (sTxA2; 0.3-30 micrograms) in the pulmonary circulation and its effect on the distribution of pressure gradients determined by the occlusion technique in isolated nonblood perfused newborn lamb lungs. The total pulmonary pressure gradient (delta Pt) was partitioned into pressure drops across the relatively indistensible arteries and veins (delta Pv) and relatively compliant vessels. We also evaluated the effects of prostacyclin (PGI2) and a Tx receptor antagonist (ONO 3708) on the sTxA2-induced pulmonary responses. Injection of sTxA2 caused a dose-related increase in the pulmonary arterial pressure, with the primary component of the increase in delta Pt (4.1 +/- 0.8 to 13.9 +/- 0.4 Torr) at 30 micrograms derived from the prominent rise in delta Pv (1.8 +/- 0.3 to 9.8 +/- 0.9 Torr). Infusion of PGI2 (0.4 microgram.kg-1.min-1) reduced the response to sTxA2 mainly by attenuating the delta Pv elevation. Infusion of ONO 3708 (100 micrograms.kg-1.min-1) completely abolished the sTxA2-induced pulmonary hypertension. Injection of sTxA2 resulted in pulmonary edema characterized by a significant increase in wet-to-dry lung weight ratio (9.13 +/- 0.35 vs. 7.15 +/- 0.41 in control lungs). The sTxA2-induced pulmonary edema was increased by PGI2 and inhibited by ONO 3708. We conclude that thromboxane-induced pulmonary hypertension is primarily produced by venoconstriction and prostacyclin may worsen the edema induced by thromboxane.
Yoshimura
K
K
Department of Medicine, University of Maryland School of Medicine, Baltimore 21201.
Tod
M L
ML
Pier
K G
KG
Rubin
L J
LJ
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D004357:Drug Synergism; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D011654:Pulmonary Edema / Q000209:etiology* / Q000503:physiopathology; D012756:Sheep; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D013928:Thromboxane A2; C037866:STA 2; D011464:Epoprostenol