본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Expression of Nitric Oxide Synthase and Endothelin-1 in Human Uterine Artery from Full-Term Pregnancies

Choi, Ook-Hwan    (Departments of Obstetrics and Gynecology, College of Medicine, Pusan National University   ); Lee, Sun-Hee    (Departments of Pharmacology, College of Medicine, Pusan National University   ); Kim, Eun-Jin    (Departments of Pharmacology, College of Medicine, Pusan National University   ); Kim, Koan-Hoi    (Departments of Pharmacology, College of Medicine, Pusan National University   ); Rhim, Byung-Yong    (Departments of Pharmacology, College of Medicine, Pusan National University  );
  • 초록

    The aim of this study was to determine the roles of ET-1 and NO on uterine blood flow in pregnancy. Uterine arteries were isolated from 17 nonpregnant and 12 pregnant women. Nonpregnant group included patients with median age of $48.6{\pm}2.3$ years who underwent hysterectomy, because of myoma. Pregnant group included patients with median age of $31.3{\pm}1.4$ years undergoing cesarean delivery. ET-1 and ET-2 induced concentration-dependent contraction in isolated nonpregnant and pregnant uterine arteries. The contractile response and maximal contraction were increased in pregnant uterine arteries. In nonpregnant uterine arteries, there was no contraction in response to ET-3, whereas pregnancy induced concentration-dependent contraction by ET-3. Tissue nitrite/nitrate level and immunohistochemical staining of eNOS and iNOS were increased in pregnant uterine arteries, compared with nonpregnant uterine arteries. In addition, the expressions of eNOS and iNOS mRNA were significantly increased in pregnancy. Moreover, contractions by ET isopeptides, including ET-1, were enhanced, and immunohistochemical staining of ET-1 and ET-1 mRNA expression was increased in pregnant uterine arteries. These results suggest that NO production by increased NOS activity, especially eNOS activity, is related to placental and uterine blood flow. Furthermore, ET-1 appears to play a pathophysiological role in pregnant complications such as hypertension.


  • 주제어

    Nitric oxide .   Endothelin-1 .   Nitric oxide synthase .   Uterine artery .   Full-term pregnancy.  

  • 참고문헌 (55)

    1. Arai H, Hori S, Aramori I, Ohkubo H, Nakanishi S. Cloning and expression of a cDNA encoding an endothelin receptor. Nature 348: 730-732, 1990 
    2. Archer S. Measurement of nitric oxide in biological models. FASEB J 7: 349-360, 1993 
    3. Battistini B, O'Donnell LJ, Warner TD, Fournier A, Farthing MJ, Vane JR. Characterization of endothelin (ET) receptors in the isolated gall bladder of the guinea-pig: evidence for an additional ET receptor subtype. Br J Pharmacol 112: 1244-1250, 1994b 
    4. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248-254, 1976 
    5. Conrad K, Vernier KA. Plasma level, urinary excretion, and metabolic production of cGMP during gestation in rats. Am J Physiol 257: R847-R853, 1989 
    6. King AJ, Brenner BM, Anderson S. Endothelin: a potent renal and systemic vasoconstrictor peptide. Am J Physiol 256: F1051- F1058, 1989 
    7. Lowe DT. Nitric oxide dysfunction in the pathophysiology of preeclampsia. Nitric Oxide 4: 441-458, 2000 
    8. Magness RR, Osei-Boaten K, Mitchell MS, Rosenfeld CR. In vitro prostacyclin production by ovine uterine and systemic arteries. J Clin Invest 76: 2206-2212, 1985 
    9. Magness RR, Shaw CE, Phernetton TM, Zheng J, Bird IM. Endothelial vasodilator production by uterine and systemic arteries. II. Pregnancy effects on NO synthase expression. Am J Physiol 272: H1730-H1740, 1997 
    10. Nelson SH, Suresh MS. Pregnancy: endothelium-dependent cholinergic dilation of human uterine arteries (Abstract D43). In: Proceedings of the annual meeting of the Society of Obstetrical Anesthesiologists and Perinatologists. San Francisco, Society of Obstetrical Anesthesiologists and Perinatologists, 1989 
    11. Pernow J. Actions of constrictor (NPY and endothelin) and dilator (substance P, CGRP and VIP) peptides on pig splenic and human skeletal muscle arteries: involvement of the endothelium. Br J Pharmacol 97: 983-989, 1989 
    12. Reilly RD, Russell PT. Neurohistochemical evidence supporting an absence of adrenergic and cholinergic innervation in the human placenta and umbilical cord. Anat Rec 188: 277-286, 1977 
    13. Sakurai T, Yanagisawa M, Takuwa Y, Miyazaki H, Kimura S, Goto K, Masaki T. Cloning of a cDNA encoding a non-isopeptideselective subtype of the endothelin receptor. Nature 348: 732- 735, 1990 
    14. Warner TD, Allcock GH, Mickley EJ, Vane JR. Characterization of endothelin receptors mediating the effects of the endothelin/ sarafotoxin peptides on autonomic neurotransmission in the rat vas deferens and guinea-pig ileum. Br J Pharmacol 110: 783- 789, 1993 
    15. Weiner CP, Martinez E, Chestnut DH, Ghodsi A. Effect of pregnancy on uterine and carotid artery response to norepinephrine, epinephrine and phenylephrine in vessels with documented functional endothelium. Am J Obstet Gynecol 161: 1605- 1610, 1989a 
    16. Weiner CP, Martinez E, Zhu LK, Ghodsi A, Chestnut D. In vitro release of endothelium-derived relaxing factor by acetylcholine is increased during the guinea pig pregnancy. Am J Obstet Gynecol 161: 1599-1605, 1989b 
    17. Dotsch J, Hogen N, Nyul Z, Hanze J, Knerr I, Kirschbaum M, Rascher W. Increase of endothelial nitric oxide synthase and endothelin-1 mRNA expression in human placenta during gestation. Eur J Obstet Gynecol Reprod Biol 97: 163-167, 2001 
    18. Anumba DO, Robson SC, Boys RJ, Ford GA. Nitric oxide activity in the peripheral vasculature during normotensive and preeclamptic pregnancy. Am J Physiol 277: H848-H854, 1999 
    19. Magness RR, Rosenfeld CR, Hassan A, Shaul PW. Endothelial vasodilator production by uterine and systemic arteries. I. Effects of ANG II on $PGI_{2}$ and NO in pregnancy. Am J Physiol 270: H1914-H1923, 1996 
    20. Nelson SH, Steinsland OS, Suresh MS, Lee NM. Pregnancy augments nitric oxide-dependent dilator response to acetylcholine in the human uterine artery. Hum Reprod 13: 1361- 1367, 1998 
    21. Steele SC, Warren AY, Johnson IR. Effect of the vascular endothelium on norepinephrine-induced contractions in uterine radial arteries from the nonpregnant and pregnant human uterus. Am J Obstet Gynecol 168: 1623-1628, 1993 
    22. Nishikawa S, Miyamoto A, Yamamoto H, Ohshika H, Kudo R. The relationship between serum nitrate and endothelin-1 concentrations in preeclampsia. Life Sci 67: 1447-1454, 2000 
    23. Nova A, Sibai BM, Barton JR, Mercer BM, Mitchell MD. Maternal plasma level of endothelin is increased in preeclampsia. Am J Obstet Gynecol 165: 724-727, 1991 
    24. Moncada S. The 1991 Ulf von Euler Lecture. The L-arginine: nitric oxide pathway. Acta Physiol Scand 145: 201-227, 1992 
    25. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J 6: 3051-3064, 1992 
    26. Nelson SH, Steinsland OS, Johnson RL, Suresh MS, Gifford A, Ehardt JS. Pregnancy-induced alterations of neurogenic constriction and dilation of human uterine artery. Am J Physiol 268: H1694-1701, 1995 
    27. Peeters LL, Grutters G, Martin CB. Distribution of cardiac output in the unstressed pregnant guinea pig. Am J Obstet Gynecol 138: 1177-1184, 1980 
    28. Rosenfeld CR, Naden RP. Uterine and nonuterine vascular responses to angiotensin II in ovine pregnancy. Am J Physiol 257: H17-H24, 1989 
    29. Saida K, Mitsui Y, Ishida N. A novel peptide, vasoactive intestinal constrictor of a new (endothelin) peptide family. J Biol Chem 264: 14613-14616, 1989 
    30. Williams DL, Jones KL, Pettibone DJ, Lis EV, Clineschmidt BV. Sarafotoxin S6c: an agonist which distinguishes between endothelin receptor subtypes. Biophys Biochem Res Commun 175: 556-561, 1991 
    31. Maggi CA, Giuliani S, Patacchini R, Rovero P, Giachetti A, Meli A. The activity of peptides of the endothelin family in various mammalian smooth muscle preparations. Eur J Pharmacol 174: 23-31, 1989 
    32. Schiff E, Ben-Baruch G, Peleg E, Goldenberg M, Rosenthal T, Alcalay M, Devir M, Mashiach S. Immunoreactive circulating endothelin-1 in normal and hypertensive pregnancies. Am J Obstet Gynecol 166: 624-628, 1992 
    33. Lippton H, Goff J, Hyman A. Effects of endothelin in the systemic and vascular beds in vivo. Eur J Pharmacol 155: 440-444, 1988 
    34. McLaughlin MK, Keve TM, Cooke R. Vascular catecholamine sensitivity during pregnancy in the ewe. Am J Obstet Gynecol 160: 47-53, 1989 
    35. Napolitano M, Miceli F, Calce A, Vacca A, Gulino A, Apa R, Lanzone A. Expression and relationship between endothelin-1 messenger ribonucleic acid (mRNA) and inducible/endothelial nitric oxide synthase mRNA isoforms from normal and preeclamptic placentas. J Clin Endocrinol Metab 85: 2318-2323, 2000 
    36. Iwata I, Takagi T, Yamaji K, Tanizawa O. Increase in the concentration of immunoreactive endothelin in human pregnancy. J Endocrinol 129: 301-307, 1991 
    37. Myatt L, Brewer AS, Brockman DE. The comparative effects of big endothelin-1, endothelin-1, and endothelin-3 in the human fetal-placental circulation. Am J Obstet Gynecol 167: 1651- 1656, 1992 
    38. Taylor RN, Varma M, Teng NN, Roberts JM. Women with preeclampsia have higher plasma endothelin levels than women with normal pregnancies. J Clin Endocrinol Metab 71: 1675- 1677, 1990 
    39. Battistini B, Warner TD, Fournier A, Vane JR. Characterization of ETB receptors mediating contractions induced by endothelin-1 or IRL 1620 in guinea-pig isolated airways: Effects of BQ-123, FR139327 or PD145065. Br J Pharmacol 111: 1009-1016, 1994a 
    40. Inoue A, Yanagisawa M, Kimura S, Yoshitoshi K, Miyauchi T, Goto K, Masaki T. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci USA 86: 2863-2867, 1989 
    41. Poston L, McCarthy AL, Ritter JM. Control of vascular resistance in the maternal and feto-placental arterial beds. Pharmacol Ther 65: 215-239, 1995 
    42. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332: 411-415, 1988 
    43. Magness RR. Endothelium-derived vasoactive substances and uterine blood vessels. Semin Perinatol 15: 68-78, 1991 
    44. Marletta MA. Nitric oxide biosynthesis and biological significance. Trends Biol Sci 14: 488-492, 1989 
    45. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [$^{15}N$]nitrate in biological fluids. Anal Biochem 126: 131-138, 1982 
    46. Conrad K, Vill M, McGuire PG, Dail WG, Davis AK. Expression of nitric oxide synthase by syncytiotrophoblast in human placental villi. FASEB J 7: 1269-1276, 1993 
    47. Fried G, Samuelson U. Endothelin and neuropeptide Y are vasoconstrictors in human uterine blood vessels. Am J Obstet Gynecol 164: 1330-1336, 1991 
    48. Griendling KK, Fuller EO, Cox RH. Pregnancy-induced changes in sheep uterine and carotid arteries. Am J Physiol 248: H658- H665, 1985 
    49. Nelson SH, Steinsland OS, Wang Y, Yallampalli C, Dong YL, Sanchez JM. Increased nitric oxide synthase activity and expression in the human uterine artery during pregnancy. Circ Res 87: 406-411, 2000 
    50. Weiner CP, Kang-Zhu L, Thompson LP, Herrig J, Chestnut DH. Effect of pregnancy on endothelium and smooth muscle: their role in reduced adrenergic sensitivity. Am J Physiol 261: H1275- H1283, 1991 
    51. Franco-Cereceda A. Endothelin- and neuropeptide Y-induced vasoconstriction of human epicardial coronary arteries in vitro. Br J Pharmacol 97: 968-972, 1989 
    52. Lees MM, Taylor SH, Scott DB, Kerr MG. A study of cardiac output at rest throughout pregnancy. J Obstet Gynaecol Br Commonw 74: 319-328, 1967 
    53. Li P, Tong C, Eisenach JC. Pregnancy and ephedrine increase the release of nitric oxide in ovine uterine arteries. Anesth Analg 82: 288-293, 1996 
    54. Lowenstein CJ, Snyder SH. Nitric oxide: a novel biologic messenger. Cell 70: 705-707, 1992 
    55. Usuki S, Saitoh T, Sawamura T, Suzuki N, Shigemitsu S, Yanagisawa M, Goto K, Onda H, Fujino M, Masaki 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 4: 85-97, 1990 
  • 이 논문을 인용한 문헌 (1)

    1. 2013. "" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 17(6): 499~503     

 저자의 다른 논문

  • Choi, Ook-Hwan (1)

    1. 2011 "14q32.33 Deletion Identified by array-CGH in a 5-year old-girl with Seizure" Journal of genetic medicine 8 (1): 62~66    
  • 김관회 (13)

  • 임병용 (27)

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
  • NDSL :
  • 대한약리학회 : 저널
  • 대한생리학회 : 저널
유료다운로드
  • 원문이 없습니다.

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기