Summers SM, Ulloa AS, Purdy RE. Endothelial role in the thoracic aorta response to hindlimb unloading in rats. Aviat Space Environ Med 2007; 78:1103–7. Background: Hindlimb unloading (HLU) is used to simulate microgravity in rats and has been shown to decrease contractile response in the abdominal aorta. The thoracic aorta has not been studied as thoroughly. Methods: Wistar and Sprague-Dawley rats were subjected to HLU for 20 d and the thoracic aortas were isolated and sectioned into 3-mm rings for the measurement of isometric force development. Concentration response curves (CRCs) to phenylephrine (PHE) were obtained in endothelium-intact and -denuded rings from both strains of rats. Acetylcholine, methylfurmethide (MFM), and sodium nitroprusside (SNP) CRCs were obtained in the Wistar rats. Results: HLU had no effect on the contractions of endothelium-intact Wistar aortas to PHE, but decreased the maximal PHE-induced contraction (2.82 ± 0.16 g Control vs. 2.18 ± 0.11 g HLU) in intact Sprague-Dawley aortas. After endothelium removal, HLU increased the contractions of Wistar, but not Sprague-Dawley, aortas to PHE (1.91 ± 0.12 g Control vs. 2.95 ± 0.13 g HLU). HLU had no effect on the relaxation to acetylcholine, but increased the sensitivity to the relaxing effects of MFM (LOG EC50 −6.96 ± 0.12 Control vs.−7.31 ± 0.17 HLU) and SNP (LOG EC50 −7.90 ± 0.15 Control vs.−8.35 ± 0.10 HLU) in the Wistar rats. Summary: It is concluded that HLU increased smooth muscle contracting and endothelium-dependent relaxing capacities equally in the Wistar aortas, and had no effect on smooth muscle, but increased endothelium-dependent relaxation, in the Sprague-Dawley aortas.