Modulation of the effects of norepinephrine uptake inhibitors on the norepinephrine-induced contractile response of the porcine uterine artery during early pregnancy.

The effects of norepinephrine (NE) uptake inhibitors on the porcine uterine artery's contractile response to NE and their potential alteration during early pregnancy (Day 13 postcoitus; day of coitus = Day 0) in comparison with the end of the luteal phase (Days 11-14; first day of behavioral estrus = Day 0) was investigated. This pregnancy time point is characterized by a transient increase in resting uterine blood flow dependent on the presence of blastocysts, an increased endometrial vascular permeability, and the beginning of the endometrial attachment of the blastocysts. A cumulative concentration-response curve (CCRC) to NE was produced in isometrically-mounted rings. Cocaine (5 microM) was used to inhibit neuronal NE uptake and hydrocortisone (30 microM) was used to inhibit extraneuronal NE uptake. Either drug alone induced a leftward shift of the CCRC to NE without affecting the maximal response. This shift had the same amplitude at the end of the luteal phase and in early pregnancy. However, the leftward shift induced by cocaine was larger than that induced by hydrocortisone only in early pregnancy, and the leftward shift induced by exposure to both hydrocortisone and cocaine was larger in early pregnancy than at the end of the luteal phase. These results suggest that a significant sensitization of the contractile response of the porcine uterine artery to NE is induced by neuronal and extraneuronal uptake inhibitors and that this effect is altered in early pregnancy, possibly reflecting the existence of a mechanism protecting the uterine artery against excessive sympathetic stimulation.