Studies have shown that maternal smoking causes intrauterine growth retardation and this may be as a result of endothelial dysfunction. It is possible that the prostaglandins may be involved in this mechanism. The aim of this study was to investigate the functional response of segments of human umbilical artery (HUA) to stable thromboxane (U46619) and prostacyclin (cicaprost) mimetics and measure the release of prostacyclin and thromboxane metabolites.
Segments of HUA were attached to pressure transducers via a cannula and perfused with Krebs (2.5% O2/8%CO2/balance N2) at 1 ml min−1. If used, indometacin was included in the perfusate at a 1 μM concentration and 5HT at 0. 1 μM (to induce tone). After equilibration agonists were added as bolus doses. Samples of perfusate were collected after 1 and 4 hours and thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α were measured using EIA kits. A minimum of 5 tissue samples (from different donors) was used in each experiment.
U46619 (0.0110 nmol) evoked a dose related constriction and cicaprost (0.00110 nmol) a dose related dilation. Smoking potentiated the response to U46619 but attenuated the response to cicaprost. TXB2 release was not significantly different between 1 and 4 hours, nor did the presence of indometacin or maternal smoking have any significant effect on release. 6-keto-prostaglandin F1α release was approximately 50 fold greater than that of TXB2. Maternal smoking had no statistically significant effect upon output but indometacin caused a significant reduction in 6-keto-prostaglandin F1α release in tissues taken from smoking and non-smoking donors.
The results of this study confirm the presence of functional thromboxane and prostacyclin receptors on the human umbilical artery. The data show that the isolated artery is capable of releasing prostacyclin and thromboxane in vitro for up to 4 hours and the ratio of production favours prostacyclin. The effects of smoking are being investigated further.
06 - 07 Nov 2006
Society for Endocrinology