Published Online
on December 9, 2002

A more recent version of this article appeared on January 1, 2003

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Submitted on May 16, 2002
Revised on May 31, 2002

A Diffusible Substance(s) Mediates Endothelium-Dependent Contractions in the Aorta of SHR

Di Yang; Michel Félétou^*; Nigel Levens; Ji Nan Zhang; and Paul M. Vanhoutte

From Jiangsu Province Hospital, First Affiliated Hospital of Nanjing Medical University (D.Y., J.N.Z.), Nanjing, Peoples Republic of China; Pharmacologie et Physico-Chimie, Université Louis Pasteur de Strasbourg (D.Y.), Illkirch, France; Institut de Recherches Servier (M.F., N.L.), Suresnes, France; and Institut de Recherches Internationales Servier (P.M.V.), Courbevoie Cedex, France.

^* To whom correspondence should be addressed. E-mail: michel.feletou{at}fr.netgrs.com.

Abstract—A modified bioassay system was designed to demonstrate the diffusible nature of endothelium-derived contracting factor(s) released by acetylcholine in the aorta of spontaneously hypertensive rat. In "sandwich"-like layered preparation, isometric tension was recorded from a bioassay strip (without endothelium) in the presence of N^G-nitro-L-arginine and tetrahydrobiopterin to selectively potentiate endothelium-dependent contractions. A donor strip (with or without endothelium) was stitched on the bioassay tissue so that it did not directly contribute to the recorded contractions. Acetylcholine induced contractions that occurred only when the donor strip was with endothelium. Superoxide dismutase did not affect but catalase and the combination of superoxide dismutase plus catalase significantly decreased the endothelium-dependent contraction. The contractions in the layered preparations were abolished when the donor strip with endothelium was treated previously with valeryl salicylate, an irreversible cyclooxygenase-1 inhibitor, but remained unaffected when the bioassay strip was treated with the compound. Previous treatment of the bioassay strip alone with S 18886 abolished the contractile response, whereas treatment of the donor strip with endothelium by the selective TP receptor antagonist only produced a moderate inhibition. These results indicate that in the aorta of spontaneously hypertensive rats, endothelium-dependent contractions to acetylcholine involve a diffusible substance(s) released by the endothelium. The production of this contracting factor(s) requires the activation of endothelial cyclooxygenase-1, and its action the activation of TP receptors on the vascular smooth muscle cells.

Key words: cyclooxygenase • endothelium-dependent contraction • tetrahydrobiopterin • free radicals • rats, spontaneously hypertensive • receptors, thromboxane

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