title: The influence of oxygen on the isolated human umbilical artery
Creators: name: MacLennan, Stephen John
Publisher: name: University of Glasgow
Year: 1986

description: This study is an investigation of two aspects of the effect of oxygen on the isolated human umbilical artery. The physiological environment of the artery, with respect to the blood, in utero, is both acidic and de-oxygenated, i.e. pH -7.28, PO2 ~15mmHg. The major part of this work uses longitudinal strips of the artery which were initially set-up under these physiological conditions. The experimental work is divided into three chapters. Chapter 1 is an assessment of the 3 main techniques used to measure smooth muscle contraction of isolated preparations, i. e. isometric and isotonic contraction, and constant flow perfusion pressure. It was found that the potency of 5-hydroxytryptamine (5-HT), bradykinin and adrenaline to cause contraction was similar using any of the techniques. At low PO2 (the physiological level) 5-HT was more potent than bradykinin while adrenaline weakly contracted only the perfused artery. The order of potency was 5-HT&gt;bradykinin»adrenaline. At high PO2 (~120mmHg) adrenaline produced constriction of the artery when assessed by any of the techniques. The order of potency was 5-HT&gt;bradykinin»adrenaline. The vasoconstrictor effect of raising the oxygen tension above the physiological level was similarly assessed and it was found that the sensitivity of the smooth muscle was similar using isometric or isotonic contraction, or constant flow perfusion pressure. However, when using the latter technique the artery required to be under longitudinal tension for oxygen to cause contraction. From this it was concluded that oxygen may act on the longitudinal muscle alone. Since the potency of 5-HT, bradykinin and adrenaline, and of raising the oxygen tension, was similar in the three techniques there seemed to be no advantage in using any one technique for assessing contraction of the longitudinal muscle, in preference to the other two. Isometric contraction was used in all subsequent experiments. This comparative study of the techniques used to assess contraction of the human umbilical artery failed to resolve differences between the potency of various agonists, as reported in the existing literature. In chapter 2 a further investigation is made of the vasoconstrictor effect of oxygen. Raising the oxygen tension above 15mmHg evoked concentration-related contractions. In the initial experiments a threshold for contraction was predicted: at pH 7.28 this was 36mmHg and the maximum response occurred at 297mmHg. However, in further experiments raising the oxygen tension from OmmHg to 15mmHg caused a contraction. This argued against a threshold for contraction. This effect of oxygen was mediated by prostaglandins: the cyclo-oxygenase inhibitor, indomethacin, inhibited oxygen-induced contractions at nanomolar concentrations. Flurbiprofen was approximately equipotent to indomethacin, while aspirin was more than 10,000 fold less potent. From a study of the influence of gestational age on the effect of oxygen it could be concluded only that the smooth muscle of the umbilical arteries, from infants at least of 27 weeks gestation, could synthesise constrictor prostaglandins since this was the earliest gestational age at which oxygen caused contraction. Only one other preparation of a lesser gestational age (26 weeks) and which was not contracted by oxygen, was examined. No significant correlation was found between gestational age and sensitivity to oxygen, or the size of the maximal oxygen-induced contraction. Umbilical arteries were similarly sensitive to 5-HT at all gestational ages which were tested, from 26 weeks to 41 weeks. In chapter 3 the receptors for 5-HT and adrenaline are characterized. At the physiological Po2, methysergide and ketanserin were potent competitive antagonists of the contractile response to 5-HT.