Roberto Simäo Mathias

Hypoxia and response of human umbilical artery strips to 5-hydroxytryptamine: Role of prostaglandin F2α

1. This article examines the effects of hypoxia on the contractile response of isolated human umbilical artery strips to 5-hydroxytryptamine (5-HT). 2. Hypoxic conditions produce a large increase in the contractile response to 5-HT without a significant alteration of the sensitivity evaluated at the level of the pD2 value. Indomethacin (10 microM) reduced hypoxia-induced potentiation of the response to 5-HT and decreased the response to the monoamine under oxygenated conditions. 1-NAME (100 microM) did not further increase the effect of hypoxia on the vessel response to 5-HT and increased the response to 5-HT under oxygenated conditions. 3. Taken together, these results suggest that, at least partially, the response of human umbilical artery strips to 5-HT depends on 5-HT release of a contracting prostanoid which is a product of the cyclooxygenase pathway. Furthermore, during hypoxia in human umbilical artery strips, there appears to be impairment of the basal production and/or release of EDRF/NO. 4. A subthreshold concentration of prostaglandin F2 alpha (1 nM) potentiates the response to 5-HT in indomethacin-pretreated umbilical artery strips. The data raise the possibility that prostaglandin F2 alpha might be the prostanoid released during hypoxia, which in turn potentiates the response of the human umbilical artery to 5-HT.

Effects of simulated myocardial ischemic conditions on the responses of isolated human umbilical artery strips to 5-hydroxytryptamine and prostaglandin F2α

1. The effects of simulated myocardial ischemic conditions on the contractile response of isolated human umbilical artery (HUA) strips to 5-hydroxytryptamine (5-HT) and prostaglandin F2 alpha (PGF2 alpha) were studied. 2. During simulated myocardial ischemic conditions the contractile response of HUA strips to 5-HT was lower than the response to the monoamine under oxygenated conditions. Under simulated ischemic conditions the response to 5-HT was further depressed by the cyclooxygenase inhibitor indomethacin (10 microM) and increased by the NO synthase inhibitor L-NAME (100 microM). 3. During simulated ischemic conditions the response of the HUA to a submaximal concentration of PGF2 alpha (3 microM) was reduced. Indomethacin (10 microM) further reduced the response to the prostanoid whereas L-NAME (100 microM) enhanced the response to PGF2 alpha. 4. It is concluded that during simulated myocardial ischemic conditions lactate negatively modulates the contractile response of HUA strips to 5-HT. Apparently, during simulated myocardial ischemic conditions in the HUA the production and/or release of EDRF/NO was not affected.

Endogenous thromboxane A2 does not contribute to the contractile response of human umbilical artery strips to 5-hydroxytryptamine

1. To investigate the possible role of endogenous thromboxane A2 (TXA2) in 5-hydroxytryptamine (5-HT)-induced contraction, human umbilical artery strips were suspended in isolated organ chambers for measurement of isometric force. 2. In endothelium intact strips, arachidonic acid (AA;1 microM) potentiates the contractile response to 5-HT, whereas the response was reduced by indomethacin (INDO;10 microM). De-endothelialized strips showed reduced responses to 5-HT. 3. Arachidonic acid-induced potentiation of the responses to 5-HT was prevented by INDO, and the TXA2 synthase inhibitor dazoxiben (DAZ;1 microM and 10 microM) was without effect on the responses to 5-HT in endothelium intact strips. 4. Taken collectively, these results suggest that, in human umbilical artery strips, the contractile response to 5-HT is at least partly dependent on the 5-HT induced release of an endothelium-derived contracting factor (EDCF), which is a cyclooxygenase metabolite. The lack of effect of DAZ indicates that TXA2 is not the EDCF released during the contractile response of human umbilical artery strips to 5-HT.