Effects of pre-eclampsia on maternal plasma, cerebrospinal fluid, and umbilical cord urotensin II concentrations: a pilot study.

BACKGROUND Urotensin II (UII) is the most potent endogenous vasoconstrictor identified to date. Pre-eclampsia is associated with arteriolar vasospasm but the precise underlying mechanism is uncertain and we hypothesized that UII concentrations might also be elevated. In this study we measured UII concentrations in maternal plasma and cerebrospinal fluid (CSF), and umbilical vein plasma from pre-eclamptic (PET) and normotensive patients undergoing elective Caesarean section under spinal or combined spinal-epidural anaesthesia. METHODS With LREC approval and informed consent we recruited two groups of 10 patients; control [mean (range) age, 29 (22-43) yr; BMI, 25 (20-32); gestation, 273 (267-281) days; mean arterial pressure (MAP) on day of delivery, 81 (75-96) mm Hg] and PET [age, 34 (22-40) yr; BMI, 25 (21-46); gestation, 253 (203-289) days; MAP on day of delivery, 106 (88-128) mm Hg]. Maternal blood and CSF samples and umbilical vein blood samples were taken. UII was extracted and concentrations measured using a radioimmunoassay. RESULTS Two plasma and two CSF samples in the control and two CSF samples in the PET group were below the assay detection limits. There were no differences in maternal plasma or CSF or umbilical vein UII concentrations between the groups. However, there was a small ( approximately 40%) but significant increase in cord UII concentrations when compared with paired plasma in the PET group. There was a weak but significant negative correlation (r=-0.4, P=0.049) between cord UII concentrations and gestation in the PET group. In addition, we observed a significant positive correlation between plasma and CSF (r(2)=+0.57, P=0.0009, n=16), plasma and cord (r(2)=+0.43, P=0.0031, n=18) and CSF and cord (r(2)=+0.32, P=0.022, n=16) UII concentrations for the whole data set. CONCLUSIONS Collectively the data indicate that UII concentrations do not increase in PET compared with controls but, in PET patients, cord UII concentrations are elevated relative to paired plasma samples. Elevated umbilical vein UII concentrations may simply indicate reduced placental viability and possibly UII metabolism as a result of reduced blood flow or possibly that the placenta is producing UII.

[1]  A. Davenport,et al.  Cellular distribution of immunoreactive urotensin-II in human tissues with evidence of increased expression in atherosclerosis and a greater constrictor response of small compared to large coronary arteries , 2004, Peptides.

[2]  C. May,et al.  Urotensin II, a novel peptide in central and peripheral cardiovascular control , 2004, Peptides.

[3]  L. Carbillon,et al.  Pathophysiology of preeclampsia: links with implantation disorders. , 2004, European journal of obstetrics, gynecology, and reproductive biology.

[4]  B. Cheung,et al.  Plasma concentration of urotensin II is raised in hypertension , 2004, Journal of hypertension.

[5]  S. Doggrell Urotensin-II and the cardiovascular system – the importance of developing modulators , 2004, Expert opinion on investigational drugs.

[6]  R. Hannan,et al.  Urotensin II: the old kid in town , 2004, Trends in Endocrinology & Metabolism.

[7]  H. Krum,et al.  Urotensin-II as a novel therapeutic target in the clinical management of cardiorenal disease. , 2004, Current opinion in investigational drugs.

[8]  D. Johns,et al.  From 'gills to pills': urotensin-II as a regulator of mammalian cardiorenal function. , 2004, Trends in pharmacological sciences.

[9]  D. Lambert,et al.  A Comparison of Cerebrospinal Fluid and Plasma Urotensin II Concentrations in Normotensive and Hypertensive Patients Undergoing Urological Surgery During Spinal Anesthesia: A Pilot Study , 2003, Anesthesia and analgesia.

[10]  C. May,et al.  Urotensin II Acts Centrally to Increase Epinephrine and ACTH Release and Cause Potent Inotropic and Chronotropic Actions , 2003, Hypertension.

[11]  S. Douglas Human urotensin-II as a novel cardiovascular target: 'heart' of the matter or simply a fishy 'tail'? , 2003, Current opinion in pharmacology.

[12]  S. Coley,et al.  The diagnosis and management of pre‐eclampsia , 2003 .

[13]  Chao-shu Tang,et al.  [Clinical study of changes of urotensin II in patients with congestive heart failure]. , 2003, Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA.

[14]  T. Dschietzig,et al.  Plasma levels and cardiovascular gene expression of urotensin-II in human heart failure , 2002, Regulatory Peptides.

[15]  I. Squire,et al.  Plasma Urotensin in Human Systolic Heart Failure , 2002, Circulation.

[16]  A. Davenport,et al.  Is urotensin‐II the new endothelin? , 2002, British journal of pharmacology.

[17]  E. Beinder,et al.  Production of vasoactive substances by human umbilical vein endothelial cells after incubation with serum from preeclamptic patients. , 2001, European journal of obstetrics, gynecology, and reproductive biology.

[18]  S. Ito,et al.  Role of urotensin II in patients on dialysis , 2001, The Lancet.

[19]  T. Sauerbruch,et al.  Increased urotensin II plasma levels in patients with cirrhosis and portal hypertension. , 2001, Journal of hepatology.

[20]  Jean-Marie Moutquin,et al.  The Classification and Diagnosis of the Hypertensive Disorders of Pregnancy: Statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP) , 2001, Hypertension in pregnancy.

[21]  S. Douglas,et al.  Human urotensin-II, the most potent mammalian vasoconstrictor identified to date, as a therapeutic target for the management of cardiovascular disease. , 2000, Trends in cardiovascular medicine.

[22]  A. Davenport,et al.  Urotensin II: fish neuropeptide catches orphan receptor. , 2000, Trends in pharmacological sciences.

[23]  H. Bern,et al.  A reference preparation for the study of active substances in the caudal neurosecretory system of teleosts. , 1969, The Journal of endocrinology.

[24]  S. Ito,et al.  Increased plasma urotensin II levels in patients with diabetes mellitus. , 2003, Clinical science.

[25]  A. Halligan,et al.  Recent developments in the pathophysiology and management of pre-eclampsia. , 1996, British journal of anaesthesia.