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      Lack of Endotoxin-lnduced Hyporesponsiveness to U46619 in Isolated Neonatal Porcine Pulmonary but Not Mesenteric Arteries

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          The effects of endotoxin from Escherichia coli on the vasoconstrictor responses to noradrenaline (10 n M–100 µ M) and the thromboxane A<sub>2</sub> analog U46619 (100 p M–1 µ M) were evaluated on isolated pulmonary and mesenteric arteries from neonatal piglets. Incubation for 20 h with endotoxin (1 µg ml<sup>–1</sup>) induced a decrease in the contractile responses to noradrenaline in both arteries (p < 0.05) which was inhibited by N<sup>G</sup>-nitro- L-arginine-methyl ester ( L-NAME, 100 µ M). 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 nitroprus-side, 8-bromo-cyclic GMP or dipyridamole than those induced by 10 µ M noradrenaline. In conclusion, endotoxin-treated pulmonary arteries exhibited decreased responses to noradrenaline due to enhanced nitric oxide release but not to the thromboxane A<sub>2</sub> 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<sup>2+</sup>-inde-pendent nitric oxide synthase induction in the lung.

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          Author and article information

          J Vasc Res
          Journal of Vascular Research
          S. Karger AG
          24 September 2008
          : 33
          : 3
          : 249-257
          aDepartment of Pharmacology, Institute of Pharmacology and Toxicology, School of Medicine, Universidad Complutense, and bDivision of Neonatology, Department of Pediatrics, Hospital Universitario S. Carlos, Madrid, Spain
          159152 J Vasc Res 1996;33:249–257
          © 1996 S. Karger AG, Basel

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          Pages: 9
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