Loss of endothelium-dependent vasodilation in the pulmonary vessels of sheep after prolonged endotoxin.
We examined the hemodynamic response of awake sheep to prolonged endotoxin infusion (10 ng.kg-1 x min-1 for 12 h) and the in vitro endothelium-dependent relaxation of pulmonary arterial vessels excised 12 h after the end of endotoxin infusion to determine whether the development of pulmonary hypertension after endotoxin is associated with loss of endothelium-dependent relaxation. In seven of nine sheep, there was a maintained increase (4-68% of baseline) in pulmonary arterial pressure 24 h after the beginning of endotoxin infusion. The greater the increase in pulmonary arterial pressure in vivo, the greater was the in vitro deficit in endothelium-dependent relaxation of the pulmonary vessels. The maximum in vitro vessel dilation was 59% for pulmonary artery rings isolated from sheep without a sustained increase in pulmonary arterial pressure 24 h after endotoxin. Prolonged endotoxin infusion did not alter the in vitro response of pulmonary arterial vessels to KCl or 10(-5) M norepinephrine. Force development, response to 10(-5) M norepinephrine, and vasodilation in response to acetylcholine were also not altered in pulmonary vessels taken from control sheep and exposed in vitro to tumor necrosis factor-alpha (400 U/ml). Our results suggest that loss of endothelium-dependent relaxation in pulmonary vessels supports the sustained pulmonary hypertension that develops after prolonged exposure to endotoxin.
Spath
J A
JA
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Sloane
P J
PJ
Gee
M H
MH
Albertine
K H
KH
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D009569:Nitric Oxide / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011651:Pulmonary Artery / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep; D013318:Stroke Volume / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine