Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.4)
Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2006, vol. 15, nr 5, September-October, p. 789–795

Publication type: original article

Language: English

Plasma and Urinary Uroguanylin in Preeclamptic and Healthy Pregnant Women and Their Fetuses

Stężenie uroguaniliny w surowicy krwi i w moczu u zdrowych kobiet ciężarnych, ciężarnych z preeklampsją oraz u ich płodów

Franciszek Kokot1,, Izabela Ulman2,, Masamitzu Nakazato3,, Tomasz Irzyniec1,4,, Andrzej Więcek1,

1 Department of Nephrology, Endocrinology, and Metabolic Diseases, Silesian University Medical School, Katowice, Poland

2 Department of Obstetrics and Gynecology, Silesian University Medical School, Katowice, Poland

3 Department of Internal Medicine, Miyazaki Medical College, Miyazaki, Japan

4 Department of Health Promotion, Silesian University Medical School, Katowice, Poland

Abstract

Background. Preeclampsia is characterized by elevated blood pressure, proteinuria, and abnormal water−electrolyte metabolism. Uroguanylin (UG) is a member of a new family of natriuretic, diuretic, and kaliuretic peptides which may indirectly influence blood pressure.
Objectives. This study aimed to establish the pathophysiological role of uroguanylin in preeclamptic and healthy pregnant women and their fetuses.
Material and Methods. Uroguanylin was measured in cubital vein blood obtained from 11 non−pregnant women, 14 preeclamptic, and 13 healthy pregnant women some minutes before delivery and in amniotic fluid and umbilical cord blood of the fetuses. In addition, UG was assessed in the urine of pregnant women collected 1–3 days before delivery. Uroguanylin was measured using the RIA method.
Results. Preeclamptic women showed significantly lower UG plasma levels than healthy pregnant women and non−pregnant women (2.9 ± 0.6 vs. 5.6 ± 0.5 and 8.2 ± 1.0 fmol/ml, respectively). In preeclamptic women the UG level in umbilical cord blood was lower (although not significantly) than in healthy pregnant women (3.4 ± 0.6 vs. 5.1 ± 0.6 fmol/ml). Urinary UG excretion in non−pregnant women (72.4 ± 19.3 pmol/day) was not significantly higher than in healthy pregnant women (51.3 ± 11.3 pmol/d), but was significantly higher than in preeclamptic women (24.2 ± 4.6 pmol/d). Finally, the UG concentration in the amniotic fluid of the preeclamptic women was significantly reduced compared with that of healthy pregnant women (41.1 ± 8.2 vs. 68.6 ± 6.0 fmol/ml).
Conclusion. Abnormal UG secretion seems to be involved in the pathogenesis of the abnormal water−electrolyte homeostasis in preeclampsia.

Streszczenie

Wprowadzenie. Preeklampsja charakteryzuje się nadciśnieniem tętniczym, białkomoczem i zaburzeniami gospodarki wodno−elektrolitowej. Uroguanilina jest nowym członkiem rodziny peptydów działających natriuretycznie i kaliuretycznie, a więc związkiem potencjalnie wpływającym na ciśnienie tętnicze krwi.
Cel pracy. Określenie roli patofizjologicznej uroguaniliny u ciężarnych zdrowych i z preeklampsją oraz u ich płodów.
Materiał i metody. Uroguanilinę oznaczono we krwi żylnej pobranej z żyły łokciowej u 11 nieciężarnych kobiet, u 14 ciężarnych z preeklampsją i 13 zdrowych ciężarnych (kilka minut przed rozwiązaniem), w płynie owodniowym ciężarnych oraz we krwi pępowinowej ich płodów. Uroguanilinę oznaczono ponadto w moczu kobiet nieciężarnych i u ciężarnych (zebranym 1–3 dni przed rozwiązaniem).
Wyniki. U ciężarnych z preeklampsją stwierdzono istotnie mniejsze stężenie uroguaniliny w osoczu krwi niż u zdrowych ciężarnych (2,9 ± 0,6 vs. 5,6 ± 0,5 vs. 8,2 ± 1,0 fmol/ml). U kobiet z preeklampsją stwierdzono ponadto mniejsze (statystycznie nieistotne) stężenie uroguaniliny we krwi pępowinowej płodów niż u zdrowych ciężarnych (3,4 ± 0,6 vs. 5,1 ± 0,6 fmol/ml). U nieciężarnych kobiet dobowe wydalanie uroguaniliny z moczem było nieistotnie większe (72,4 ± 19,3 pmol/d) niż u zdrowych ciężarnych (51,3 ± 11,3 pmol/d), lecz znamiennie większe niż u ciężarnych z preeklampsją (24,2 ± 4,6 pmol/d). Stężenie uroguaniliny w płynie owodniowym ciężarnych z preeklampsją było istotnie mniejsze niż u zdrowych ciężarnych (41,1 ± 8,2 vs. 68,6 ± 6 fmol/ml).
Wnioski. Udział nieprawidłowej sekrecji uroguaniliny w patogenezie zaburzeń gospodarki wodno−elektrolitowej u ciężarnych z preeklampsją jest prawdopodobny.

Key words

preeclampsia, hypertension, uroguanylin

Słowa kluczowe

preeklampsja, nadciśnienie, uroguanilina

References (49)

  1. Higgins JR, de Swiet M: Blood pressure measurement and classification in pregnancy. Lancet 2001, 357, 131–135.
  2. Roberts JM, Cooper DW: Pathogenesis and genetics of preeclampsia. Lancet 2001, 357, 53–56.
  3. Esplin MS, Fausett MD, Fraser A, Kerber R, Mineau G, Carrillo J: Paternal and maternal component of the predisposition to preeclampsia. N Engl J Med 2001, 344, 867–872.
  4. Dekker GA, Sibai BM: Etiology and pathogenesis of preeclampsia: current concepts. Am J Obstet Gynecol 1998, 179, 1359–1375.
  5. Kokot F: Starvation in the midst of plenty – the problem of volaemia in pregnancy. Nephrol Dial Transplant 1997, 12, 388–391.
  6. Lindheimer MD, Akbari A: The kidney and hypertension in pregnancy. In: Hypertension: a Companion to Brenner and Rector’s The Kidney. Eds.: Oparil S and Weber MA. WB Saunders Comp., St Louis 2000, 688–701.
  7. Brown MA, Zammit VC, Lowe SA: Capillary permeability and extracellular fluid volumes in pregnancy induced hypertension. Clin Sci 1989, 77, 599–604.
  8. Currie MG, Fok KF, Kato J, Moore RJ, Hamra FK, Duffin KL: Guanylin: an endogenous activator of intestinal guanylate cyclase. Proc Natl Acad Sci USA 1992, 89, 947–951.
  9. Hamra FK, Forte LR, Eber SL et al.: Uroguanylin: structure and activity of a second endogenous peptide that stimulates intestinal guanylate cyclase. Proc Natl Acad Sci USA 1993, 90, 10464–10468.
  10. Kita T, Smith CE, Fok KF et al.: Characterization of human uroguanylin: a member of the guanylin peptide family. Am J Physiol 1994, 266, F342–F348.
  11. Forte LR, Eber SL, Fan X et al.: Lymphoguanylin: cloning and characterization of a unique member of the guanylin peptide family. Endocrinology 1999, 140, 1800–1806.
  12. Forte LR, Fan X, Hamra FK: Salt and water homeostasis: uroguanylin is a circulating peptide hormone with natriuretic activity. Am J Kidney Dis 1996, 28, 296–304.
  13. Krause WJ, London RM, Freeman RH, Forte LR: The guanylin and uroguanylin peptide hormones and their receptors. Acta Anat Basel 1997, 160, 213–231.
  14. Forte LR, Curie MG: Guanylin: a peptide regulator of epithelial transport. FASEB J 1995, 9, 643–650.
  15. Forte LR, London RM, Freeman RH, Krause WJ: Guanylin peptides: renal actions mediated by cyclic GMP. Am J Renal Physiol 2000, 278, F180–F191.
  16. Kinoshita H, Fujimoto S, Nakazato M et al.: Urine and plasma levels of uroguanylin and its molecular forms in renal diseases. Kidney Int 1997, 52, 1028–1034.
  17. Kinoshita H, Fujimoto S, Fukae A, Yokota N, Hisanaga S, Nakazato M: Plasma and urine levels of uroguanylin, a new natriuretic peptide, in nephrotic syndrome. Nephron 1999, 81, 160–164.
  18. Kokot F, Stupnicki R: Radioimmunological and radiocompetitive methods used in clinics. 2nd ed. PZWLWarsaw 1986, 22–33.
  19. Hill O, Cetin Y, Cieslak A, Magert HJ, Forssman WG: A new human guanylate cyclase−activating peptide (GCAP−II, uroguanylin): Precursor cDNA and colonic expression. Biochim Biophys Acta 1995, 1253, 146–149.
  20. Cetin Y, Forssman WG: GCAP−II: Isolation and characterization of the circulating form of human uroguanylin. FEBS Lett 1995, 374, 34–38.
  21. Fonteles MC, Greenberg RN, Monteiro HS, Currie MG, Forte LR: Natriuretic and kaliuretic activities of guanylin and uroguanylin in the isolated perfused rat kidney. Am J Physiol 1998, 275, F191–F197.
  22. Leitman DC, Waldman SA, Murad F: Regulation of particulate guanylate cyclase by natriuretic peptides and Escherichia coli heart−stable enterotoxin. Adv Pharmacol 1994, 26, 67–86.
  23. Nakazato M, Yamaguchi H, Date Y et al.: Tissue distribution, cellular source, and structural analysis of rat immunoreactive uroguanylin. Endocrinology 1998, 139, 5247–5254.
  24. Fan X, Hamra FK, Freeman RH et al.: Uroguanylin: Cloning of preprouroguanylin cDNA, mRNA expression in the intestine and heart, and isolation of uroguanylin and prouroguanylin from plasma. Biochem Biophys Res Commun 1996, 219, 457–462.
  25. Li Z, Perkins AG, Peters MF, Campa MJ, Goy MF: Purification, cDNA sequence, and tissue distribution of rat uroguanylin. Regul Pept 1997, 68, 45–56.
  26. Fan X, Hamra FK, London RM et al.: Structure and activity of uroguanylin and guanylin from the intestine and urine of rats. Am J Physiol 1997, 273, E957–E964.
  27. Whitaker TL, Witte DP, Scott MC, Cohen MB: Uroguanylin and guanylin: distinct but overlapping patterns of messenger RNA expression in mouse intestine. Gastroenterology 1997, 113, 1000–1006.
  28. Fan X, Wang Y, London RM et al.: Signaling pathways for guanylin and uroguanylin in the digestive, renal, central nervous, reproductive, and lymphoid systems. Endocrinology 1997, 138, 4636–4648.
  29. Miyazato M, Nakazato M, Matsukura S et al.: Uroguanylin gene expression in the alimentary tract and extragastrointestinal tissue. FEBS Lett 1996, 398, 170–174.
  30. Date Y, Nakazato M, Yamaguchi H et al.: Enterochromaffin−like cells: A cellular source of uroguanylin in rat stomach. Endocrinology 1999, 140, 2398–2404.
  31. Kulaksiz H, Cetin Y: Uroguanylin and guanylate cyclase C in the human pancreas: expression and mutuality of ligand/receptor localization as indicators of intracellular paracrine signaling pathways. J Endocrinol 2001, 170, 267–275.
  32. Cui L, Blanchard RK, Cousins RJ: Dietary zinc deficiency increases uroguanylin accumulation in rat kidney. Kidney Intern 2001, 59, 1424–1431.
  33. London RM, Eber SL, Visweswariah SS et al.: Structure and activity of OK GC: a kidney receptor guanylate cyclase activated by guanylin peptides. Am J Physiol 1999, 276, F882–F891.
  34. Kokot F, Ficek R: Guanylins – are they of nephrological relevance? Nephron 2000, 84, 201–205.
  35. Forte LR, London RM, Freeman RH, Krause WJ: Guanylin peptide: renal actions mediated by cyclic GMP. Am J Renal Physiol 2000, 278, F180–F191.
  36. Hamra FK, Eber SL, Chin DT et al.: Regulation of intestinal uroguanylin/guanylin receptor mediated responses by mucosal acidity. Proc Natl Acad Sci USA 1997, 94, 2705–2710.
  37. Joo NS, London RM, Kim HD et al.: Regulation of intestinal Cl– and HCO3 – secretion by uroguanylin. Am J Physiol 1998, 274, G633–G644.
  38. Greenberg RN, Hill M, Crytzer J et al.: Comparison of effects of uroguanylin, guanylin, and Escherichia coli heat stable enterotoxin STa in mouse intestine and kidney: evidence that uroguanylin is an intestinal natriuretic hormone. J Invest Med 1997, 45, 276–282.
  39. Hamra FK, Fan X, Krause WJ et al.: Prouroguanylin and proguanylin: Purification from colon, structure and modulation of bioactivity by proteases. Endocrinology 1996, 137, 257–265.
  40. Carrithers SL, Hill MJ, Johnson BR et al.: Renal effects of uroguanylin and guanylin in vivo. Braz J Med Biol Res. 1999, 32, 1337–1344.
  41. Sindić A, Velic A, Basoglu C et al.: Uroguanylin and guanylin regulate transport of mouse cortical collecting duct independent of guanylate cyclase C. Kidney Intern. 2005, 68, 1008–1017.
  42. Semrad CE: Guanylin: where it’s at! Why’s it there? Gastroenterology 1997, 113, 1036–1038.
  43. Giannella RA: Escherichia coli heat−stable enterotoxins, guanylins, and their receptors: what are they and what do they do? J Lab Clin Med 1995, 125, 173–183.
  44. Kinoshita H, Nakazato M, Yamaguchi H et al.: Increased plasma guanylin levels in patients with impaired renal function. Clin Nephrol 1997, 47, 28–32.
  45. Fukae H, Kimoshita H, Fujimoto S et al.: Plasma concentration of uroguanylin in patients on maintenance dialysis therapy. Nephron 2000, 84, 206–210.
  46. Carrithers SL, Eber SL, Forte LR, Greenberg RN: Increased urinary excretion of uroguanylin in patients with congestive heart failure. Am J. Physiol Heart Circ Physiol 2000, 278, 538–547.
  47. Kokot F, Nakazato M, Adamczak M et al.: Plasma and urinary uroguanylin in patients with essential hypertension – relationship to plasma renin activity. Proceedings in Nephrology Publisher House “Russian Physicians”, Moscow 2001, 55–65 (in Russian).
  48. Buhimshi JA, San Martin−Clark O, Aguan K, Thompson LP, Weiner CP: Differential alterations in responsiveness in particulate and soluble guanylate cyclases in guinea pig myometrium. Am J Obstet Gynecol 2000, 183, 1512–1519.
  49. Itoh H, Sagawa N, Hasegawa M et al.: Expression of biologically active receptors of natriuretic peptides in the human uterus during pregnancy. Biochem Biophys Res Commun 1994, 203, 602–607.