RELAXANT EFFECTS OF BENZODIAZEPINES ON ISOLATED HUMAN UMBILICAL ARTERIES AND VEINS

1 Human umbilical arterial rings precontracted with 40 mM KCl were relaxed in a concentration-dependent manner (6-1 00 muM) by the benzodiazepines (BZDs) Ro 5-4864, diazepam and clonazepam. 2 Pre-incubation with the central BZD antagonist Ro 15-1788 (10 muM) for 10 min did not prevent the reductions in KCl-induced responses caused by different concentrations of either clonazepam or diazepam in the umbilical arteries. On the other hand, the putative peripheral BZD antagonist. PK 11195, was as potent as the peripheral agonist Ro 5-4864 in relaxing KCl-contracted arterial rings. 3 Contractions of the human umbilical rings induced by 1 muM 5-hydroxytryptamine (5-HT) were diminished by 6-100 muM Ro 5-4864 as well as by 6-100 muM diazepam. 4 Diazepam and Ro 5-4864 also induced relaxation of human umbilical veins precontracted with 40 mm KCl. The latter effect was not modified by the removal of the endothelium. 5 It is concluded that BZDs interfere with responses elicited through the activation of either voltage-operated (KCl) or receptor-operated (5-HT) calcium channels in the human umbilical vasculature. Although the clinical significance of these in vitro studies is unknown, they should be taken into account whenever high doses of BZDs are administered at the end of pregnancy.