Skip to main content
SpringerLink
Log in

The Relationship of Plasma Volume, Sympathetic Tone, and Proinflammatory Cytokines in Young Healthy Nonpregnant Women

  • Published:
Reproductive Sciences Aims and scope Submit manuscript

An Erratum to this article was published on 01 April 2014

This article has been updated

Abstract

Objective

Preeclampsia has been associated with elevated proinflammatory markers, increased sympathetic activity, and decreased plasma volume (PV). We hypothesized that these associations would be identified in women prior to a first pregnancy.

Methods

We studied 76 healthy nulligravid participants measuring the proinflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). Plasma volume was measured in supine position and corrected for body mass index (BMI). We examined supine plasma levels of epinephrine and norepinephrine and blood pressure response to Valsalva maneuver to quantify sympathetic activation. We then examined the association of PV and sympathetic activity with proinflammatory cytokines with P < .05 accepted for significance.

Results

CRP was significantly increased in participants with lowest PV/BMI quartile when compared to middle 2 quartiles and highest quartile (analysis of variance [ANOVA], P = .037). We found no significant association of PV/BMI with either IL-6 or TNF-a. Both plasma epinephrine concentration (r = .29, P = .02) and the late phase II (phase II_L) blood pressure response to Valsalva maneuver (r = .44, P < .0001) were associated with serum IL-6 concentrations.

Conclusions

Low PV is associated with increased CRP levels and increased sympathetic tone is linked to elevated IL-6 concentration in young nonpregnant women. These findings represent elements of a nonpregnancy phenotype that parallels the findings observed in preeclampsia and in women at risk for ischemic cardiovascular disease. This suggests that the relationships observed during preeclampsia, which have been associated with placental pathology, may predate pregnancy and be independent of placental activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Change history

  • 30 December 2014

    In the above-referenced article, Dr. Reem M. Sallam, MBBS, MSc, PhD, should have appeared as the fourth author, for significant contributions to project design and conducting critical aspects of the research.

    The corrected reference for the article is:

    Bernstein, IM, Damron, D, Schonberg, AL, Sallam, RM, Shapiro, R. The relationship of plasma volume, sympathetic tone, and proinflammatory cytokines in young healthy nonpregnant women. Reprod Sci. 2009;16;980–985.

    Dr. Sallam’s affiliation at the time of the study was with the Department of Pathology, University of Vermont College of Medicine, Burlington, VT, USA. Currently, her affiliations are with the Clinical Chemistry Unit of the Department of Pathology, and the Obesity Research Center, King Saud University College of Medicine, Riyadh, Saudi Arabia; and the Department of Medical Biochemistry and Molecular Biology, Ain Shams University Faculty of Medicine, Cairo, Egypt.

References

  1. ACOG Practice Bulletin. Diagnosis and management of preeclampsia and eclampsia. No. 33, January 2002.

  2. Gallery ED, Hunyor SN, Gyory AZ. Plasma volume contraction: a significant factor in both pregnancy-associated hypertension (preeclampsia) and chronic hypertension in pregnancy. Quart J Med. 1979;48(192):593–602.

    CAS  PubMed  Google Scholar 

  3. Soffronoff EC, Kaufmann BM, Connaughton JF. Intravascular volume determinations and fetal outcome in hypertensive diseases of pregnancy. Am J Obstet Gynecol. 1977;127(1):4–9.

    Article  CAS  Google Scholar 

  4. Silver HM, Seebeck M, Carlson R. Comparison of total blood volume in normal, preeclamptic and non-proteinuric gestational hypertensive disease by simultaneous measurement of red blood cell and plasma volumes. Am J Obstet Gynecol. 1998;179(1):87–93.

    Article  CAS  Google Scholar 

  5. Yang CC, Chao TC, Kuo TB, Yin CS, Chen HI. Preeclamptic pregnancy is associated with increased sympathetic and decreased parasympathetic control of HR. Am J Physiol. 2000;278(4):H1269–H1273.

    CAS  Google Scholar 

  6. Lewinsky RM, Riskin-Mashiah S. Autonomic imbalance in preeclampsia: evidence for increased sympathetic tone in response to the supine-pressor test. Obstet Gynecol. 1999; 91(6):935–939.

  7. Davey DA, Macnab MF. Plasma adrenaline, noradrenaline, and dopamine in pregnancy hypertension. Br J Obstet Gynecol. 1981;88(6):611–618.

    Article  CAS  Google Scholar 

  8. Schobel HP, Fischer T, Heuszar K, Geiger H, Schmieder RE. Preeclampsia—a state of sympathetic over-activity. New Engl J Med. 1996;335(20):1480–1485.

    Article  CAS  Google Scholar 

  9. Kupferminc MJ, Peaceman AM, Aderka D, Wallach D, Socol ML. Soluble tumor necrosis factor receptors and interleukin-6 levels in patients with severe preeclampsia. Obstet Gynecol. 1996;88(3):420–427.

    Article  CAS  Google Scholar 

  10. Benyo DF, Smarason A, Redman CWG, Sims C, Conrad KP. Expression of inflammatory cytokines in placentas from women with preeclampsia. J Clin Endocrinol Metab. 2001; 86(6):2505–2512.

  11. Granger JP. Inflammatory cytokines, vascular function, and hypertension. Am J Physiol Regul Integr Comp Physiol. 2004;286(6):R989–R990.

    Article  CAS  Google Scholar 

  12. Jonsdottir LS, Arngrimsson R, Geirsson RT, Sigvaldason H, Sigfusson N. Death rates from ischemic heart disease in women with a history of hypertension in pregnancy. Acta Obstet Gynecol Scand. 1995;74(10):772–776.

    Article  CAS  Google Scholar 

  13. Walraven CV, Mamdani M, Cohn A, Katib Y, Walker M, Rodger MA. Risk of subsequent thromboembolism for patients with preeclampsia. BMJ. 2003;326(7393):791–792.

    Article  Google Scholar 

  14. Wilson BJ, Watson MS, Prescott GJ, et al. Hypertensive disorders of pregnancy and risk of hypertension and stroke in later life: results from a cohort study. BMJ. 2003; 326(7394):845–851.

  15. Danesch J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary artery disease. JAMA. 1998;279(18):1477–1482.

    Article  Google Scholar 

  16. Nissen SE, Tuzcu EM, Schoenhagen P, et al. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. New Engl J Med. 2005;352(1):29–38.

    Article  CAS  Google Scholar 

  17. Bernstein IM, Meyer MC, Osol G, Ward K. Intolerance to volume expansion: A theorized mechanism for the development of preeclampsia. Obstet Gynecol. 1998;92(2):306–308.

    CAS  PubMed  Google Scholar 

  18. Damron DP, Bouchard BA, Shapiro RE, Schonberg AL, Bernstein IM. Platelet activation, sympathetic tone, and plasma volume in nulligravid women of reproductive age. Obstet Gynecol. 2004;103(5 pt 1):931–936.

    Article  Google Scholar 

  19. Bernstein IM, Shapiro R, Whitsel A, Schonberg A. Relationship of plasma volume to sympathetic tone in nulliparous women. Am J Obstet Gynecol. 2003;188(4):938–942.

    Article  Google Scholar 

  20. Vorchheimer DA, Becker R. Platelets in atherothrombosis. Mayo Clin Proc. 2006;81(1):59–68.

    Article  CAS  Google Scholar 

  21. Heusch G. Alpha-adrenergic mechanisms in myocardial ischemia. Circulation. 1990;81(1):1–13.

    Article  CAS  Google Scholar 

  22. Aardenburg R, Spaanderman MEA, Ekhart TH, van Eijndhoven HW, van der Hrijden OWH, Peeters LLH. Low plasma volume following pregnancy complicated by preeclampsia predisposes for hypertensive disease in a next pregnancy. BJOG. 2003;110(11):1001–1006.

    Article  Google Scholar 

  23. Spaanderman MEA, Aardenburg R, Ekhart THA, et al. Non-pregnant circulatory volume status predicts subsequent pregnancy outcome in normotensive thrombophilic formerly preeclamptic women. Eur J Obstet Gynecol Reprod Med. 2001; 95(2):218–221.

  24. Aardenburg R, Spaanderman ME, van Eijndhoven HW, de Leeuw PW, Peeters LL. A low plasma volume in formerly preeclamptic women predisposes to the recurrence of hypertensive complications in the next pregnancy. J Soc Gynecol Investig. 2006;13(8):598–603.

    Article  Google Scholar 

  25. Copeland KC, Kenney FA, Sreekumaran Nair K. Heated dorsal hand vein sampling for metabolic studies: a reappraisal. Am J Physiol. 1992;263(5 pt 1):E1010–E1014.

    CAS  PubMed  Google Scholar 

  26. Jiang NS, Machacek D, Wadel OP. Further study on the two-column plasma catecholamine assay. Mayo Clin Proc. 1976;51(2):112–116.

    CAS  PubMed  Google Scholar 

  27. El-Sayed H, Goodal SR, Hainsworth R. Reevaluation of Evans blue dye dilution method of plasma volume measurement. Clin Lab Haematol. 1995;17(2):189–194.

    PubMed  Google Scholar 

  28. Bernstein IM, Ziegler W, Stirewalt WS, Brumsted J, Ward K. Angiotensinogen genotype and plasma volume in nulligravid women. Obstet Gynecol. 1998;92(2):171–173.

    CAS  PubMed  Google Scholar 

  29. Denq JC, O’Brien PC, Low PA. Normative data on phases of the Valsalva maneuver. J Clin Neuro. 1998;15(6):535–540.

    Article  CAS  Google Scholar 

  30. Tjoa ML, van Vogt JMG, Blankenstein MA, Oudejans CBM, van Wijk IJ. Elevated C-reactive protein levels during first trimester of pregnancy are indicative of preeclampsia and intrauterine growth restriction. J Reprod Immunol. 2003;59(1):29–37.

    Article  CAS  Google Scholar 

  31. Courtar DA, Spaanderman ME, Aardenburg R, Janssen BJ, Peeters LL. Low plasma volume coincides with sympathetic hyperactivity and reduced baroreflex sensitivity in formerly preeclamptic patients. J Soc Gynecol Investig. 2006;13(1):48–52.

    Article  Google Scholar 

  32. Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary artery disease: meta-analyses of prospective studies. JAMA. 1998;279(18):1477–1482.

    Article  CAS  Google Scholar 

  33. Cushman M, Arnold AM, Psaty BM, et al. C-reactive protein and the 10-year incidence of coronary heart disease in older men and women: the cardiovascular health study. Circulation. 2005;112(1):25–31.

    Article  CAS  Google Scholar 

  34. Tracy RP. Inflammation, the metabolic syndrome and cardiovascular risk. Int J Clin Pract Suppl. 2003;(134):10–17.

  35. Zieske AW, Tracy RP, McMahan CA, et al;. Pathobiological Determinants of Atherosclerosis in Youth Research Group. Elevated serum C-reactive protein levels and advanced atherosclerosis in youth. Arterioscler Thromb Vasc Biol. 2005; 25(6):1237–1243.

  36. Kamat SG, Kleiman NS. Platelets and platelet inhibitors in acute myocardial infarction. Cardiology Clin. 1995;13(3):435–447.

    Article  CAS  Google Scholar 

  37. Schomig A, Richardt G. Cardiac sympathetic activity in myocardial ischemia: release and effects of noradrenaline. Basic Res Cardiol. 1990;85(suppl 1):9–30.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Obstetrics and Gynecology, University of Vermont College of Medicine, 05405, Burlington, VT, United States

    Ira M. Bernstein MD, Dana Damron MD & Adrienne L. Schonberg RN

  2. Departments of Neurology, University of Vermont College of Medicine, Burlington, Vermont, United States

    Robert Shapiro MD, PhD

Authors
  1. Ira M. Bernstein MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dana Damron MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adrienne L. Schonberg RN
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert Shapiro MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ira M. Bernstein MD.

Additional information

This study was supported by NIH R0–1 HL 71944 and GCRC MO-1 RR109.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bernstein, I.M., Damron, D., Schonberg, A.L. et al. The Relationship of Plasma Volume, Sympathetic Tone, and Proinflammatory Cytokines in Young Healthy Nonpregnant Women. Reprod. Sci. 16, 980–985 (2009). https://doi.org/10.1177/1933719109338876

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719109338876

Key words

Search

Navigation