Sustained effects of endothelin-1 on rabbit, dog, and rat pulmonary circulations.
Effects of endothelin-1 (10(-8) M) on the pulmonary vascular resistance-compliance profile were examined in isolated blood-perfused rabbit, dog, and rat lungs using occlusion techniques. Capillary permeability was assessed by filtration coefficient (Kfc). Cyclooxygenase products were assessed by radioimmunoassay. In rabbit lungs, endothelin-1 increased all resistances except large vein; ibuprofen reversed the constriction. Endothelin-1 decreased total vascular compliance (CT), which was reversed by ibuprofen. Cyclooxygenase products were unchanged by endothelin-1 or endothelin-1 plus ibuprofen. In dog lungs, large vein resistance increased after endothelin-1; ibuprofen increased large arterial resistance. Endothelin-1 decreased CT and middle compartment compliance, and endothelin-1 plus ibuprofen decreased large vessel compliance (CLV). Ibuprofen reversed the endothelin-1 increase in plasma 6-oxo-prostaglandin F1 alpha. In rat lungs, ibuprofen reversed the endothelin-1 increase in small arterial resistance. Endothelin-1 decreased CLV, and endothelin-1 plus ibuprofen returned the compliance to baseline values. Ibuprofen potentiated the endothelin-1 increase in plasma prostanoids. Endothelin-1 plus indomethacin increased vascular resistance and blocked prostaglandin production. Kfc was increased only in rat lung after endothelin-1 plus ibuprofen. In summary, endothelin-1 increased pulmonary vascular resistance, which was attenuated by prostacyclin in dogs and rats. In rabbits, the resistance increase was reversed by ibuprofen.
Barnard
J W
JW
Department of Physiology, College of Medicine, University of South Alabama, Mobile 36688.
Barman
S A
SA
Adkins
W K
WK
Longenecker
G L
GL
Taylor
A E
AE
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D015237:Dinoprost / Q000097:blood; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction
D016232:Endothelins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D007213:Indomethacin