Hypoxia and response of human umbilical artery strips to 5-hydroxytryptamine: role of prostaglandin F2 alpha.
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.
De Moraes
S
S
Department of Pharmacology, University of São Paulo, Butantan, Brazil. SDMORAES@BIOMED.ICB2.USP.BR
Carvalho
J C
JC
Cavalcante
M T
MT
Mathias
R S
RS
D015687:Cell Hypoxia / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology*; D014469:Umbilical Arteries / Q000187:drug effects* / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D012701:Serotonin; D015237:Dinoprost; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin