CARDIOVASCULAR AND RESPIRATORY ACTIONS OF U50,488H IN THE UNANESTHETIZED OVINE FETUS

In an effort to evaluate the feasibility of K-opioid receptor agonists for use in pregnancy, we have investigated the actions of U50,488H yl -N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamid on cardiovascular and respiratory control in the unanaesthetized ovine foetus. intravenous administration of U50,488H (1.0 mg/kg) to the foetus resulted in an im mediate increase in foetal blood pressure (P < 0.0001) and heart rate (P < 0.0001) which lasted 15 min, followed by a prolonged loss of hear t rate variability for up to 3 h. There was also a significant suppres sion of foetal breathing movements for 2-3 h (P < 0.008). Pretreatment with naloxone (12 mg/h) completely blocked the hypertensive and tachy cardiac response to U50,488H, but was unable to prevent the loss of va riation in heart rate or respiratory depression. These data suggest th at U50,488H can exert direct cardiovascular and respiratory actions in the ovine foetus via both opioid and non-opioid mechanisms. The nalox one-insensitive suppression of foetal breathing would severely limit t he use of U50,488H as an obstetrical analgesic.