Mini-symposium: The pathogenesis of pre-eclampsia| Volume 9, ISSUE 4, P183-189, December 1999

Vascular reactivity in pregnancy and pre-eclampsia

  • J.C. Brocklesby
    Division of Obstetrics and Gynaecology, School of Human Development, University of Nottingham, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK
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  • E. Kieran
    Division of Obstetrics and Gynaecology, School of Human Development, University of Nottingham, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK
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  • P.N. Baker
    Division of Obstetrics and Gynaecology, School of Human Development, University of Nottingham, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK
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      During pregnancy, dramatic changes occur in maternal physiology to accommodate the growing conceptus. Nowhere are these changes more evident than in the cardiovascular system. Blood volume and cardiac output increase by 40–50%. These increases have occurred by the second trimester and remain elevated until after parturition. Blood pressure throughout pregnancy remains low, secondary to a reduced peripheral resistance. However, in pre-eclampsia, total peripheral resistance increases, causing the blood pressure to rise. It has been postulated that the changes in vascular reactivity observed in both normal pregnancy and pre-eclampsia are caused by alterations in the vascular endothelium.
      All blood vessels within the vasculature are lined by a monolayer of flattened, rhomboid-shaped cells termed the endothelium. For many years these cells were considered to be a passive barrier between blood and the underlying vasculature. However, in 1980 Furchgott et al. demonstrated that if blood vessels were denuded of endothelium they were incapable of vasorelaxation.1This observation and the development of techniques for cell culture have led to much research in the field of endothelial cell biology. Endothelial cells offer a unique interface between the intra-and extra-vascular environment and have a diverse function in normal physiology and pathology, including the regulation of angiogenesis, immune responses and inflammation, as well as in the maintenance of vascular tone. This review will examine the evidence for altered agonist-induced vascular reactivity in pregnancy and pre-eclampsia, and the mechanisms responsible for these alterations.
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        • Furchgott R.F.
        • Zawadski J.V.
        The obligatory role of endothelial cells in the relaxation of smooth muscle by acetylcholine.
        Nature,. 1980; 288: 373-376
        • Gant N.
        • Chand S.
        • Worley R.
        • Whalley P.
        • Crosby U.
        • Macdonald P.
        A Clinical test useful for predicting the development of acute hypertension in pregnancy.
        Am J Obstet Gyecol. 1973; 120: 1-7
        • MacCarthy J.
        • Taylor P.
        • Graves J.
        • Raju S.
        • Poston L.
        Endothelium-dependent relaxation of human resistance arteries in pregnancy.
        Am Obstet Gynecol. 1993; 171: 1309-1315
        • Pascoal I.F.
        • Lindheimer M.D.
        • Nalbantian-Brandt C.
        • Umans J.G.
        Pre-eclampsia selectively impairs endothelium-dependent relaxation and leads to oscillatory activity in small omental arteries.
        J Clin Invest. 1998; 101: 464-470
        • Ashworth J.R.
        • Warren A.Y.
        • Baker P.N.
        • Johnson I.R.
        A comparison of endothelium-dependent relaxation in omental and myometrial resistance arteries in pregnant and nonpregnant women.
        Am J Obstet Gynecology. 1996; 175: 1307-1312
        • Kublickiene K-R.
        • Kublicas M.
        • Lindblom B.
        • Lunell N-O.
        • Nisell H.
        A comparison of myogenic and endothelial properties of myometrial and omental resistance vessels in late pregnancy.
        Am J Obstet Gynecol. 1997; 176: 560-566
        • Svane D.
        • Skajaa K.
        • Andersson K-E.
        • Forman A.
        Vascular responses in term pregnant and non-pregnant human uterus.
        Placenta. 1991; 12: 47-54
        • Steele S.C.
        • Warren A.Y.
        • Johnson I.R.
        Effect of the vascular endothelium on norepinephrine-induced contractions in uterine radial arteries from the nonpregnant and pregnant human uterus.
        Am J Obstet Gynecol. 1993; 168: 1623-1628
        • Kyle P.M.
        • Campbell S.
        • Buckley D.
        A comparison of the inactive urinary kallikrein:creatinine ratio and the angiotensin sensitivity test for the prediction of pre-eclampsia [see comments].
        Br J Obstet Gynaecol. 1996; 103: 981-987
        • Ashworth J.R.
        • Warren A.Y.
        • Baker P.N.
        • Johnson I.R.
        Loss of endothelium-dependent relaxation in myometrial resistance arteries in pre-eclampsia.
        Br J Obstet Gynaecol. 1997; 104: 1152-1158
        • Lewis P.
        • Boylan P.
        • Friedman L.
        • Hensby C.
        • Downing I.
        Prostacyclin in pregnancy.
        BMJ. 1980; 280: 1581-1582
        • Goodman R.
        • Killam A.
        • Brash A.
        • Branch R.
        Prostacyclin production during pregnancy: comparison of production during normal pregnancy and pregnancy complicated by hypertension.
        Am J Obstet Gynecol. 1982; 142: 817-822
        • Ylikorkala O.
        • Kirkinen P.
        • Viinikka L.
        Maternal plasma prostacyclin concentration in pre-eclampsia and other pregnancy complications.
        Br J Obstet Gynaecol. 1981; 88: 968-972
        • Palmer R.M.
        • Ferrige A.G.
        • Moncada S.
        Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor.
        Nature. 1987; 327: 524-526
        • Ignarro L.J.
        • Buga G.M.
        • Wood K.S.
        • Byrns R.E.
        • Chaudhuri G.
        Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.
        Proc Natl Acad Sci USA. 1987; 84: 9265-9269
        • Rees D.D.
        • Palmer R.M.
        • Moncada S.
        Role of endothelium-derived nitric oxide in the regulation of blood pressure.
        Proc Natl Acad Sci USA. 1989; 86: 3375-3378
        • Vallance P.
        • Collier J.G.
        • Moncada S.
        Effect of endothelium-dervied nitric oxide on peripheral arteriolar tone in man.
        Lancet. 1989; 2: 997-1000
        • Conrad K.P.
        • Vernier K.A.
        Plasma level, urinary excretion, and metabolic production of cGMP during gestation in rats.
        Am J Physiol. 1989; 257: R847-R853
        • Conrad K.P.
        • Joffe G.M.
        • Kruszyns H.
        Identification of increased nitric oxide biosynthesis during pregnancy in rats.
        FASAB. 1993; 7: 566-571
        • Kopp L.
        • Paraddiz G.
        • Tucci J.
        Urinary excretion of cyclic 3′–5′-adenosine monophosphate and cyclic 3′–5′-guanosine monophosphate during and after pregnancy.
        J Clin Endocrinol Metab. 1977; 25: 631-636
        • Sala C.
        • Campise M.
        • Ambroso G.
        • Motta T.
        • Zanchetti A.
        • Morganti A.
        Atrial natiuretic factor and hemodynamic changes during normal human pregnancy.
        Hypertension. 1995; 25: 631-636
        • Seligman S.P.
        • Buyon J.P.
        • Clancy R.M.
        • Young B.K.
        • Abramson S.B.
        The role of nitric oxide in the pathogenesis of pre-eclampsia.
        Am J Obstet Gynecol. 1994; 171: 944-948
        • Smarason A.K.
        • Allman K.G.
        • Young D.
        • Redman C.W.
        Elevated levels of serum nitrate, a stable end product of nitric oxide, in women with pre-eclampsia.
        Br J Obstet Gynaecol. 1997; 104: 538-543
        • Myatt L.
        • Brewer A.
        • Prada J.
        Nitric oxide synthaetase in normotensive pregnancy: measurement of urinary nitrates.
        Society for Gynaecological Investigation. 1992;
        • Brown M.
        • Tibben E.
        • Zammit V.
        • Cario G.
        • Carlton M.
        Ntirc oxide excretion in normal and hypertensive pregnancies.
        Hypertension in Pregnancy. 1995; 14: 319-326
        • Kenny L.
        • Baker P.
        • Randall M.
        • Kendall D.
        • Dunn W.
        Endothelium dependent relaxation of myometrial resistance arteries in pregnancy is mediated by endothelium-derived hyperpolarising factor.
        J Soc Gynecol Invest. 1999; 6: 228A
        • Gerber R.T.
        • Anwar M.A.
        • Poston L.
        Enhanced acetylcholine induced relaxation in small mesenteric arteries from pregnant rats: an important role for endothelium-derived hyperpolarizing factor (EDHF).
        Br J Pharmacol. 1998; 125: 455-460
        • Usuki S.
        • Saitoh T.
        • Sawamura T.
        Increased maternal plasma concentration of endothelin-1 during labor pain or on delivery and the existence of a large amount of endothelin-1 in amniotic fluid.
        Gynecol Endocrinol. 1990; 4: 85-97
        • Florijn K.W.
        • Derkx F.H.
        • Visser W.
        Plasma immunoreactive endothelin-1 in pregnant women with and without pre-eclampsia.
        J Cardiovasc Pharmacol. 1991; 17(suppl 7): S446-S448
        • Schiff E.
        • Ben-Baruch G.
        • Peleg E.
        Immunoreactive circulating endothelin-1 in normal and hypertensive pregnancies.
        Am J Obstet Gynecol. 1992; 166: 624-628
        • Sudo N.
        • Kamoi K.
        • Ishibashi M.
        • Yamaji T.
        Plasma endothelin-1 and big endothelin-1 levels in women with pre-eclampsia.
        Acta Endocrinol (Copenh). 1993; 129: 114-120
        • Yamaguchi M.
        • Mori N.
        6-Keto prostaglandin F1 alpha, thromboxane B2, and 13,14-dihydro-15-keto prostaglandin F concentrations of normotensive and preeclamptic patients during pregnancy, delivery, and the postpartum period.
        Am J Obstet Gynecol. 1985; 151: 121-127
        • Barden A.
        • Beilin L.J.
        • Ritchie J.
        • Walters B.N.
        • Michael C.A.
        Plasma and urinary endothelin 1, prostacyclin metabolites and platelet consumption in pre-eclampsia and essential hypertensive pregnancy.
        Blood Press. 1994; 3: 38-46
        • Scafer W.
        • Tielsch J.
        • Casper F.
        • Seufert R.
        • Zahradnik H.
        Urinary excretion of 6-keto-PGF1 alpha TxB2 abd PGE2 in a rat animal model of pre-eclampsia.
        Prostaglandins. 1993; 46: 167-175
        • Baker P.N.
        • Davidge S.T.
        • Barankiewicz J.
        • Roberts J.M.
        Plasma of preeclamptic women stimulates and then inhibits endothelial prostacyclin.
        Hypertension. 1996; 27: 56-61
        • Brown M.A.
        • Tibben E.
        • Zammit V.C.
        • Cario G.M.
        • Carlton M.A.
        Nitric oxide excretion in normal and hypertensive pregnancies.
        Hypertension in Pregnancy. 1995; 14: 319-326
        • Davidge S.T.
        • Stranko C.P.
        • Roberts J.M.
        Urine but not plasma nitric oxide metabolites are decreased in women with pre-eclampsia.
        Am J Obstet Gynecol. 1996; 174: 1008-1013
        • Baker P.N.
        • Davidge S.T.
        • Roberts J.M.
        Plasma from women with pre-eclampsia increases endothelial cell nitric oxide production.
        Hypertension. 1995; 26: 244-248
        • Roggensack A.M.
        • Zhang Y.
        • Davidge S.T.
        Evidence for peroxynitrite formation in the vasculature of women with pre-eclampsia.
        Hypertension. 1999; 33: 83-89
        • Taylor R.N.
        • Varma M.
        • Teng N.N.
        • Roberts J.M.
        Women with pre-eclampsia have higher plasma endothelin levels than women with normal pregnancies.
        J Clin Endocrinol Metab. 1990; 71: 1675-1677
        • Tsunoda K.
        • Abe K.
        • Yoshinaga K.
        Maternal and umbilical venous levels of endothelin in women with pre-eclampsia.
        J Hum Hypertens. 1992; 6: 61-64
        • Otani S.
        • Usuki S.
        • Saitoh T.
        Comparison of endothelin-1 concentrations in normal and complicated pregnancies.
        J Cardiovasc Pharmacol. 1991; 17: S308-S312