HUMAN PLASMA-DERIVED MATERIAL WITH CLONIDINE DISPLACING SUBSTANCE (CDS)-LIKE PROPERTIES CONTRACTS THE ISOLATED RAT AORTA

1 The biological activity of a plasma-derived, clonidine displacing substance (CDS)-like material was tested on isolated rat aortic rings and compared to that of clonidine, an imidazoline with alpha-2-adrenoceptor agonist properties. 2 The CDS-like material was partially purified from expired human blood. This product inhibited in a dose-dependent manner the binding of [H-3]-clonidine to rat brain membranes with a ki of 0.87 +/- 0.4 u ml-1, without affecting the binding of the alpha-1-antagonist, [H-3]-WB4101. 3 When the CDS-like material (0.14-6 u ml-1) was applied to the bathing medium of isolated rat aortic rings, it caused dose-dependent contractions with an EC50 of 1.0 +/- 0.18 u ml-1. Clonidine also dose-dependently contracted rat aortic rings (EC50, 1.1 +/- 0.24 x 10(-7) M). The maximal tension developed in response to clonidine, however, was higher (1.37 +/- 0.15 g) compared to that developed in response to the CDS-like material (0.92 +/- 0.12 g). 4 Contractions induced by both CDS-like material and clonidine were antagonized by 5 x 10(-7) M rauwolscine, an alpha-2-adrenoceptor antagonist. Prazosin, an alpha-1-adrenoceptor antagonist, at 10(-8) M, greatly reduced contractions caused by clonidine while leaving those caused by CDS-like material unaffected. 5 The CDS-like material failed to alter the tension of intact or endothelium-denuded rat aortic rings which had been precontracted with methoxamine. Clonidine on the other hand, caused dose-dependent relaxations in intact, though not in denuded, precontracted rat aortic rings. 6 These results indicate that a human plasma-derived CDS-like material interacts with the rat aorta to cause contraction by a mechanism which may not be identical to that of clonidine. Furthermore, unlike clonidine, CDS-like material does not appear to affect endothelium-derived releasing factor/nitric oxide (EDRF/NO) production from the aortic endothelium. Therefore, in addition to CDS being an important central modulator of blood pressure, a plasma-derived CDS-like material may regulate vascular tone at the peripheral level.