Comparative 5-HT2A-receptor and alpha1-adrenoceptor antagonistic activity of an ergoline LEK-8829 and its degradation product LEK-1814 in rabbit isolated aorta

Abstract

Endothelium derived relaxing factor (EDRF) is a local modulator of vasomotor tone in most blood vessels. Reversed vein grafts in several animal models do not produce EDRF when stimulated, and have been shown to have altered responses to several vasoconstrictors. The preservation of EDRF production and vasomotor function in in situ vein grafts was examined in this study. In situ vein grafts of the right carotid artery were performed in five mongrel dogs using external jugular vein. The contralateral jugular vein was used as a control. The vessels were harvested after 6 weeks and rings from the central portion of each vessel studied in vitro in an organ bath. Following cumulative dose response curves to noradrenaline, the rings were precontracted with the estimated ED50 (50% effective dose) dose of noradrenaline, and cumulative doses of acetylcholine added to induce EDRF release. The vein grafts were hypersensitive to noradrenaline, the ED50 being reduced from 8.7 ± 2.7 × 10−7m in the jugular veins to 1.7 ± 0.7 × 10−7m in the vein grafts (p < 0.05). All of the jugular vein segments relaxed in response to acetylcholine with a mean maximal relaxation of 42 ± 6% of precontraction. None of the vein graft segments relaxed in response to acetylcholine despite the presence of an intact endothelium on scanning electron microscopy, but did relax in response to calcium ionophore. The results indicate that in situ vein grafts, like reversed grafts, fail to produce EDRF in response to acetylcholine. The grafts are also hypersensitive to noradrenaline. It is concluded that the in situ technique confers no benefits to the graft in terms of preservation of endothelial or vasomotor function.