Sexton, Anita-Jane; (1996) Local control of human umbilical vessel tone. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis examines the influence of the vascular endothelium on the local control of human feto-placental vascular tone and how these influences may vary with gestation. Electron microscopic studies have revealed that human umbilical vessels are devoid of nerves throughout gestation. Structural changes in the arterial and venous wall could be detected throughout gestation. The presence of a subpopulation of endothelial cells containing nitric oxide synthase (NOS)-like immunoreactivity was identified only in late pregnancy. The umbilical artery and vein, from both early and late pregnancy, did not relax to acetylcholine (ACh), adenosine 5'-triphosphate (ATP), substance P (SP) and calcium ionophore A23187, known to be endothelium-dependent vasodilators, but did relax to sodium nitroprusside (SNP). Using the method of in vitro pharmacology, it was shown that 5- hydroxytryptamine (5-HT), histamine and endothclin-1 (ET-1) arc all vasoconstrictors in early and late pregnancy, acting independently of the endothelium in late pregnancy. 5-HT was shown to mediate constriction of the human umbilical artery and vein by an action on 5-HT1 and 5-HT2 receptors. This contraction was found to be significantly more potent in early pregnancy. Evidence for endothelial cells as a source of 5-HT, histamine and ET-1 was found only in late pregnancy and is presented with electron immunocytochemical localization of these substances in the endothelial cells of the human umbilical artery and vein. A physiological role for these substances is suggested since exogenous addition of these substances had an effect on isolated vessel preparations. ATP and [alpha],[beta]-methylene ATP ([alpha],[beta]-MeATP) induced vasconstriction in the human umbilical artery from early and late pregnancy, acting independently of the endothelium in late pregnancy. 2-Methylthio ATP (2-MeSATP) and ATP did not initiate vasodilatation of the umbilical artery or vein from either early or late pregnancy. Receptor binding studies and autoradiography have identified the presence of P2X-purinoceptors on the smooth muscle of umbilical arteries and veins from early and late pregnancy. The results reported here contribute to the understanding of the local control mechanisms regulating feto-placental vascular tone. Of particular interest is the fact that umbilical endothelial cells do not directly modify blood flow throughout gestation, but substances shown to be localised in umbilical endothelial cells may be released to act in an autocrine/paracrine manner.

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