Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1985 Dec;76(6):2206–2212. doi: 10.1172/JCI112229

In vitro prostacyclin production by ovine uterine and systemic arteries. Effects of angiotensin II.

R R Magness, K Osei-Boaten, M D Mitchell, C R Rosenfeld
PMCID: PMC424343  PMID: 3908484

Abstract

Normal pregnancy is associated with reduced systemic pressor responses to infused angiotensin II (ANG II); furthermore, the uterine vascular bed is even less responsive to vasoconstriction by ANG II than the systemic vasculature overall. The mechanism(s) for this refractoriness remains unknown. To determine if vessel production of prostacyclin may be responsible, uterine and omental artery segments were obtained from four groups of sheep, nonpregnant (NP), pregnant (P; 131 +/- 4 d), early postpartum (2.2 +/- 0.4 d), and late postpartum (16 +/- 2 d), and incubated in Krebs-Henseleit alone or with ANG II in the absence or presence of Saralasin. Prostacyclin was measured as 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Synthesis of 6-keto-PGF1 alpha was de novo, since aspirin inhibited its formation. P and early uterine arteries produced more 6-keto-PGF1 alpha than NP and late vessels (P less than 0.05): 386 +/- 60 (X +/- SE) and 175 +/- 23 vs. 32 +/- 5 and 18 +/- 4 pg/mg X h, respectively. A similar relationship was observed for omental arteries: 101 +/- 14 and 74 +/- 14 vs. 36 +/- 10 and 22 +/- 4 pg/mg X h, respectively. Furthermore, synthesis by arteries from P and early animals was greater in uterine than omental vessels (P less than 0.05); this was not observed in NP or late vessels. ANG II increased 6-keto-PGF1 alpha production 107 +/- 20% and 92 +/- 16% in P and early uterine arteries only; the threshold dose was between 5 X 10(-11) and 5 X 10(-9) M ANG II. This ANG II-induced increase in 6-keto-PGF1 alpha by uterine arteries was inhibited by Saralasin, which by itself had no effect. During pregnancy, the reduced systemic pressor response to ANG II and the even greater refractoriness of the uterine vascular bed may be reflective of vessel production of the potent vasodilator, prostacyclin. Furthermore, in the uterine vasculature, this antagonism may be potentiated by specific ANG II receptor-mediated increases in prostacyclin.

Full text

PDF
2208

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ABDUL-KARIM R., ASSALIN S. Pressor response to angiotonin in pregnant and nonpregnant women. Am J Obstet Gynecol. 1961 Aug;82:246–251. doi: 10.1016/0002-9378(61)90053-9. [DOI] [PubMed] [Google Scholar]
  2. Berssenbrugge A. D., Goodfriend T. L., Ball D. L., Rankin J. H. The effect of pregnancy on the angiotensin II pressor response in the rabbit. Am J Obstet Gynecol. 1980 Mar 15;136(6):762–767. doi: 10.1016/0002-9378(80)90453-6. [DOI] [PubMed] [Google Scholar]
  3. Blair-West J. R., Coghlan J. P., Denton D. A., Scoggins B. A., Wintour E. M. The pressor effect of angiotensin II in pregnant sheep. Aust J Exp Biol Med Sci. 1972 Dec;50(6):739–744. doi: 10.1038/icb.1972.67. [DOI] [PubMed] [Google Scholar]
  4. CHESLEY L. C., TALLEDO E., BOHLER C. S., ZUSPAN F. P. VASCULAR REACTIVITY TO ANGIOTENSIN II AND NOREPINEPHRINE IN PREGNANT WOMEN. Am J Obstet Gynecol. 1965 Mar 15;91:837–842. doi: 10.1016/0002-9378(65)90462-x. [DOI] [PubMed] [Google Scholar]
  5. Chang W. C., Nakao J., Orimo H., Murota S. I. Stimulation of prostaglandin cyclooxygenase and prostacyclin synthetase activities by estradiol in rat aortic smooth muscle cells. Biochim Biophys Acta. 1980 Dec 5;620(3):472–482. [PubMed] [Google Scholar]
  6. Chang W. C., Nakao J., Orimo H., Murota S. Stimulation of prostacyclin biosynthetic activity by estradiol in rat aortic smooth muscle cells in culture. Biochim Biophys Acta. 1980 Jul 14;619(1):107–118. [PubMed] [Google Scholar]
  7. Clark K. E., Austin J. E., Stys S. J. Effect of bisenoic prostaglandins on the uterine vasculature of the nonpregnant sheep. Prostaglandins. 1981 Sep;22(3):333–348. doi: 10.1016/0090-6980(81)90096-4. [DOI] [PubMed] [Google Scholar]
  8. Dadak C., Hoche C., Sinzinger H. Prostacyclin synthesis stimulating plasma factor in pregnancy and puerperium. Obstet Gynecol. 1984 Jul;64(1):72–76. [PubMed] [Google Scholar]
  9. Douglas J. R., Jr, Johnson E. M., Jr, Marshall G. R., Jaffe B. M., Needleman P. Stimulation of splenic prostaglandin release by angiotensin and specific inhibition by cysteine 8-AII. Prostaglandins. 1973 Jan;3(1):67–74. doi: 10.1016/0090-6980(73)90138-x. [DOI] [PubMed] [Google Scholar]
  10. Everett R. B., Worley R. J., MacDonald P. C., Gant N. F. Effect of prostaglandin synthetase inhibitors on pressor response to angiotensin II in human pregnancy. J Clin Endocrinol Metab. 1978 Jun;46(6):1007–1010. doi: 10.1210/jcem-46-6-1007. [DOI] [PubMed] [Google Scholar]
  11. Ferris T. F., Stein J. H., Kauffman J. Uterine blood flow and uterine renin secretion. J Clin Invest. 1972 Nov;51(11):2827–2833. doi: 10.1172/JCI107105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gant N. F., Chand S., Whalley P. J., MacDonald P. C. The nature of pressor responsiveness to angiotensin II in human pregnancy. Obstet Gynecol. 1974 Jun;43(6):854–854. [PubMed] [Google Scholar]
  13. Gant N. F., Daley G. L., Chand S., Whalley P. J., MacDonald P. C. A study of angiotensin II pressor response throughout primigravid pregnancy. J Clin Invest. 1973 Nov;52(11):2682–2689. doi: 10.1172/JCI107462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goodman R. P., Killam A. P., Brash A. R., Branch R. A. Prostacyclin production during pregnancy: comparison of production during normal pregnancy and pregnancy complicated by hypertension. Am J Obstet Gynecol. 1982 Apr 1;142(7):817–822. doi: 10.1016/s0002-9378(16)32525-x. [DOI] [PubMed] [Google Scholar]
  15. Gough E. D., Dyer D. C. Responses of isolated human uterine arteries to vasoactive drugs. Am J Obstet Gynecol. 1971 Jul 1;110(5):625–629. doi: 10.1016/0002-9378(71)90241-9. [DOI] [PubMed] [Google Scholar]
  16. Hettiaratchi E. S., Pickford M. The effect of oestrogen and progesterone on the pressor action of angiotensin in the rat. J Physiol. 1968 May;196(2):447–451. doi: 10.1113/jphysiol.1968.sp008517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lewis P. J., Boylan P., Friedman L. A., Hensby C. N., Downing I. Prostacyclin in pregnancy. Br Med J. 1980 Jun 28;280(6231):1581–1582. doi: 10.1136/bmj.280.6231.1581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matsuura S., Naden R. P., Gant N. F., Jr, Parker C. R., Jr, Rosenfeld C. R. Effect of hypertonic saline on vascular responses to angiotensin II in pregnancy. Am J Obstet Gynecol. 1983 Oct 1;147(3):231–240. doi: 10.1016/0002-9378(83)91103-1. [DOI] [PubMed] [Google Scholar]
  19. Matsuura S., Naden R. P., Gant N. F., Jr, Parker C. R., Jr, Rosenfeld C. R. Effect of volume expansion on pressor response to angiotensin II in pregnant ewes. Am J Physiol. 1981 Jun;240(6):H908–H913. doi: 10.1152/ajpheart.1981.240.6.H908. [DOI] [PubMed] [Google Scholar]
  20. McGiff J. C., Crowshaw K., Terragno N. A., Lonigro A. J. Release of a prostaglandin-like substance into renal venous blood in response to angiotensin II. Circ Res. 1970 Jul;27(1 Suppl 1):121–130. [PubMed] [Google Scholar]
  21. McLaughlin M. K., Brennan S. C., Chez R. A. Effects of indomethacin on sheep uteroplacental circulations and sensitivity to angiotensin II. Am J Obstet Gynecol. 1978 Oct 15;132(4):430–435. doi: 10.1016/0002-9378(78)90780-9. [DOI] [PubMed] [Google Scholar]
  22. Mitchell M. D., Brunt J., Clover L., Walker D. W. Prostaglandins in the umbilical and uterine circulations during late pregnancy in the ewe. J Reprod Fertil. 1980 Mar;58(2):283–287. doi: 10.1530/jrf.0.0580283. [DOI] [PubMed] [Google Scholar]
  23. Mitchell M. D., Ellwood D. A., Anderson A. B., Turnbull A. C. Elevated concentrations of 6-keto-prostaglandin F1alpha in fetal and maternal plasma and in amniotic fluid during ovine parturition. Prostaglandins Med. 1978 Sep;1(3):265–266. doi: 10.1016/0161-4630(78)90112-x. [DOI] [PubMed] [Google Scholar]
  24. Naden R. P., Coultrup S., Arant B. S., Rosenfeld C. R. Metabolic clearance of angiotensin II in pregnant and nonpregnant sheep. Am J Physiol. 1985 Jul;249(1 Pt 1):E49–E55. doi: 10.1152/ajpendo.1985.249.1.E49. [DOI] [PubMed] [Google Scholar]
  25. Naden R. P., Gant N. F., Jr, Rosenfeld C. R. The pressor response to angiotensin II: the roles of peripheral and cardiac responses in pregnant and nonpregnant sheep. Am J Obstet Gynecol. 1984 Feb 15;148(4):450–457. doi: 10.1016/0002-9378(84)90725-7. [DOI] [PubMed] [Google Scholar]
  26. Naden R. P., Rosenfeld C. R. Effect of angiotensin II on uterine and systemic vasculature in pregnant sheep. J Clin Invest. 1981 Aug;68(2):468–474. doi: 10.1172/JCI110277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rosenfeld C. R. Distribution of cardiac output in ovine pregnancy. Am J Physiol. 1977 Mar;232(3):H231–H235. doi: 10.1152/ajpheart.1977.232.3.H231. [DOI] [PubMed] [Google Scholar]
  28. Rosenfeld C. R., Gant N. F., Jr The chronically instrumental ewe: a model for studying vascular reactivity to angiotensin II in pregnancy. J Clin Invest. 1981 Feb;67(2):486–492. doi: 10.1172/JCI110057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rosenfeld C. R., Jackson G. M. Estrogen-induced refractoriness to the pressor effects of infused angiotensin II. Am J Obstet Gynecol. 1984 Feb 15;148(4):429–435. doi: 10.1016/0002-9378(84)90721-x. [DOI] [PubMed] [Google Scholar]
  30. Rosenfeld C. R., Morriss F. H., Jr, Battaglia F. C., Makowski E. L., Meschia G. Effect of estradiol-17beta on blood flow to reproductive and nonreproductive tissues in pregnant ewes. Am J Obstet Gynecol. 1976 Mar 15;124(6):618–629. doi: 10.1016/0002-9378(76)90064-8. [DOI] [PubMed] [Google Scholar]
  31. Rosenfeld C. R. Responses of reproductive and nonreproductive tissues to 17 beta-estradiol during ovine puerperium. Am J Physiol. 1980 Nov;239(5):E333–E339. doi: 10.1152/ajpendo.1980.239.5.E333. [DOI] [PubMed] [Google Scholar]
  32. Satoh H., Hosono M., Satoh S. Distinctive effect of angiotensin II on prostaglandin production in dog renal and femoral arteries. Prostaglandins. 1984 Jun;27(6):807–820. doi: 10.1016/s0090-6980(84)80002-7. [DOI] [PubMed] [Google Scholar]
  33. Schwarz R., Retzke U. Cardiovascular response to infusions of angiotensin II in pregnant women. Obstet Gynecol. 1971 Nov;38(5):714–718. [PubMed] [Google Scholar]
  34. Schölkens B. A., Gehring D., Schlotte V., Weithmann U. Evening primrose oil, a dietary prostaglandin precursor, diminishes vascular reactivity to renin and angiotensin II in rats. Prostaglandins Leukot Med. 1982 Mar;8(3):273–285. doi: 10.1016/0262-1746(82)90050-6. [DOI] [PubMed] [Google Scholar]
  35. Seillan C., Ody C., Russo-Marie F., Duval D. Differential effects of sex steroids on prostaglandin secretion by male and female cultured piglet endothelial cells. Prostaglandins. 1983 Jul;26(1):3–12. doi: 10.1016/0090-6980(83)90069-2. [DOI] [PubMed] [Google Scholar]
  36. Siddiqi T. A., Austin J. E., Holroyd J. C., Clark K. E. Modulation of angiotensin II pressor responsiveness by circulating levels of angiotensin II in pregnant sheep. Am J Obstet Gynecol. 1983 Feb 15;145(4):458–464. doi: 10.1016/0002-9378(83)90317-4. [DOI] [PubMed] [Google Scholar]
  37. Strickland D. M., Brennecke S. P., Mitchell M. D. Measurement of 13,14-dihydro-15-keto-prostaglandin F2 alpha and 6-keto-prostaglandin F1 alpha in plasma by radioimmunoassay without prior extraction or chromatography. Prostaglandins Leukot Med. 1982 Nov;9(5):491–493. doi: 10.1016/0262-1746(82)90029-4. [DOI] [PubMed] [Google Scholar]
  38. Terragno D. A., Crowshaw K., Terragno N. A., McGiff J. C. Prostaglandin synthesis by bovine mesenteric arteries and veins. Circ Res. 1975 Jun;36(6 Suppl 1):76–80. doi: 10.1161/01.res.36.6.76. [DOI] [PubMed] [Google Scholar]
  39. Terragno N. A., Terragno D. A., Pacholczyk D., McGiff J. C. Prostaglandins and the regulation of uterine blood flow in pregnancy. Nature. 1974 May 3;249(452):57–58. doi: 10.1038/249057a0. [DOI] [PubMed] [Google Scholar]
  40. Tulenko T. N. The actions of prostaglandins and cyclo-oxygenase inhibition on the resistance vessels supplying the human fetal placenta. Prostaglandins. 1981 Jun;21(6):1033–1043. doi: 10.1016/0090-6980(81)90171-4. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES