Human plasma-derived material with clonidine displacing substance (CDS)-like properties contracts the isolated rat...

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 [3H]-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, [3H]-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.(ABSTRACT TRUNCATED AT 250 WORDS)