Decreased arterial wall prostaglandin production in neonatal calves with severe chronic pulmonary hypertension.
Neonatal calves exposed to chronic hypobaric hypoxia develop severe pulmonary hypertension associated with altered vascular reactivity, cellular proliferation, and increased elastin and collagen production. We hypothesized that prostaglandin (PG) production would be decreased in the pulmonary arterial vessel wall of these calves. Further, because of the possibility that the hemodynamic stresses of hypoxic pulmonary hypertension might change along the longitudinal axis of the pulmonary circulation, we measured prostaglandin synthetic capability in tissues isolated from proximal pulmonary artery, distal pulmonary artery, and pulmonary vein. We found that PGI2 production was decreased in both proximal and distal pulmonary artery rings isolated from pulmonary hypertensive calves compared to controls. PGI2 production was greater in distal than in proximal lobar pulmonary artery. In contrast, pulmonary veins from hypertensive calves, which are protected from the hemodynamic stress of pulmonary arterial hypertension, did not demonstrate altered PGI2 production compared to controls. PGE2 production was also decreased in proximal hypertensive pulmonary arterial rings as compared to controls. To determine if this decrease in vessel wall production of prostaglandins was due to changes in cellular prostaglandin production, we studied prostaglandin production by the three major cell types comprising hypertensive and control arteries. Endothelial cells cultured from hypertensive main pulmonary artery produced less PGI2 than did those from control artery, and there appeared to be a shift from PGI2 production to PGE2 production in endothelial cells isolated from hypertensive artery. Explanted advential fibroblasts from hypertensive artery produced less PGE2 than did controls. Smooth muscle cell PGI2 production did not differ between cells isolated from hypertensive and control arteries in these brief 30-min incubations. We conclude that there is a relative deficit in PGI2 and PGE2 production in the pulmonary arteries of calves with hypoxia-induced pulmonary hypertension and speculate that this contributes to altered vascular tone and vessel remodeling.
Badesch
D B
DB
Cardiovascular and Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver 80262.
Orton
E C
EC
Zapp
L M
LM
Westcott
J Y
JY
Hester
J
J
Voelkel
N F
NF
Stenmark
K R
KR
D000818:Animals; D000831:Animals, Newborn; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism*; D011667:Pulmonary Veins / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis
D000001:Calcimycin; D013929:Thromboxane B2; D011464:Epoprostenol; D015232:Dinoprostone