Lack of endotoxin-induced hyporesponsiveness to U46619 in isolated neonatal porcine pulmonary but not mesenteric arteries.
The effects of endotoxin from Escherichia coli on the vasoconstrictor responses to noradrenaline (10 nM-100 microM) and the thromboxane A2 analog U46619 (100 pM-1 microM) were evaluated on isolated pulmonary and mesenteric arteries from neonatal piglets. Incubation for 20 h with endotoxin (1 microgram ml-1) induced a decrease in the contractile responses to noradrenaline in both arteries (p < 0.05) which was inhibited by NG-nitro-L-arginine-methyl ester (L-NAME, 100 microM). Endotoxin-treated mesenteric arteries also showed a reduction of the maximal contractions induced by U46619 (p < 0.05) and this effect was inhibited by L-NAME. In contrast, the contractile responses to U46619 were similar in control and endotoxin-treated pulmonary arteries. In endothelium-denuded pulmonary rings, endotoxin was also unable to modify the contractile responses to U46619. In pulmonary rings, the contractions induced by U46619 (100 nM) were much less sensitive to sodium nitroprusside, 8-bromo-cyclic GMP or dipyridamole than those induced by 10 microM noradrenaline. In conclusion, endotoxin-treated pulmonary arteries exhibited decreased responses to noradrenaline due to enhanced nitric oxide release but not to the thromboxane A2 analog U46619. This lack of hyporesponsiveness to U46619 in pulmonary arteries may be attributed to a relative insensitivity to nitric oxide. The absence of pulmonary hyporesponsiveness to U46619 may explain why pulmonary hypertension occurs in septic shock despite Ca(2+)-independent nitric oxide synthase induction in the lung.
Pérez-Vizcaíno
F
F
Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
Villamor
E
E
Fernandez del Pozo
B
B
Moro
M
M
Tamargo
J
J
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D000831:Animals, Newborn; D004731:Endotoxins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects*; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004731:Endotoxins; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D009638:Norepinephrine