Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1981 Aug;68(2):468–474. doi: 10.1172/JCI110277

Effect of angiotensin II on uterine and systemic vasculature in pregnant sheep.

R P Naden, C R Rosenfeld
PMCID: PMC370820  PMID: 7263862

Abstract

The response of uteroplacental blood flow (UBF) to angiotensin II is controversial. Moreover, the relationship of the uterine and systemic responses to infused angiotensin II is not well understood. Thus, in eight chronically instrumented, near-term pregnant sheep, we have determined the relationships between the dose and duration of constant systemic infusions of angiotensin II ([Val5] ANG II) and changes in UBF, uterine vascular resistance (UVR), mean arterial pressure (MAP), and systemic vascular resistance (SVR). [Val5] ANG II caused dose-dependent increases in UVR and MAP at all doses studied (P less than 0.05). The response in UBF was bidirectional, with increases at doses less than or equal to 1.15 microgram/min and decreases at greater than or equal to 2.29 micrograms/min (P less than 0.05). Increases in UBP occurred when the relative rise (delta) in MAP greater than delta UVR, whereas UBF was unchanged when delta MAP = delta UVR and decreased when delta MAP less than delta UVR. SVR also rose in a dose-dependent fashion (P less than 0.05); delta SVR was greater than delta UVR at doses less than or equal to 2.29 micrograms [Val5] ANG II/min (P less than 0.01). In studies of the effect of duration of [Val5] ANG II infusions, UBF increased at all doses during the 1st min, followed by stabilization at 4--5 min, with eventual decreases at doses greater than or equal to 2.29 micrograms/min and increases at doses less than 2.29 micrograms/min. The relationship between the changes in MAP and UVR to the response of UBF was as noted above. It is evident that (a) [Val5] NAG II is uterine vasoconstrictor, (b) changes in UBF are dependent upon relative changes in perfusion pressure and UVR, which in turn are dependent upon both the dose and duration of a [Val5] ANG II infusion, and (c) the uteroplacental vasculature is relatively refractory to the vasoconstricting effects of low doses of [Val5] ANG II.

Full text

PDF
474

Selected References

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

  1. ASSALI N. S., WESTERSTEN A. Regional flow-pressure relationship in response to angiotensin in the intact dog and sheep. Circ Res. 1961 Jan;9:189–193. doi: 10.1161/01.res.9.1.189. [DOI] [PubMed] [Google Scholar]
  2. Anderson D., Berssenbrugge A., Phernetton T., Rankin J. H. Effect of angiotensin II on ovine placental blood flow. Proc Soc Exp Biol Med. 1978 May;158(1):54–58. doi: 10.3181/00379727-158-40138. [DOI] [PubMed] [Google Scholar]
  3. Carretero O. A. The properties and possible role of renin-like enzymes in the uterus and amniotic gluid. Perspect Nephrol Hypertens. 1976;5:293–306. [PubMed] [Google Scholar]
  4. Cohen D. M., Steinberger S. J., Swan J. F., Disalvo J. Angiotensin II increases uterine vascular resistance in pregnant and nonpregnant rabbits. Proc Soc Exp Biol Med. 1977 Apr;154(4):597–601. doi: 10.3181/00379727-154-39726. [DOI] [PubMed] [Google Scholar]
  5. Edelstone D. I., Botti J. J., Mueller-Heubach E., Caritis S. N. Response of the circulation of pregnant sheep to angiotensin and norepinephrine before and after dexamethasone. Am J Obstet Gynecol. 1978 Mar 15;130(6):689–692. doi: 10.1016/0002-9378(78)90329-0. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. GREISS F. C., Jr, VAN WILKES EFFECTS OF SYMPATHOMIMETIC DRUGS AND ANGIOTENSIN ON THE UTERINE VASCULAR BED. Obstet Gynecol. 1964 Jun;23:925–930. [PubMed] [Google Scholar]
  8. Gant N. F., Madden J. D., Chand S., Worley R. J., Strong J. D., MacDonald P. C. Metabolic clearance rate of dehydroisoandrosterone sulfate. V. Studies of essential hypertension complicating pregnancy. Obstet Gynecol. 1976 Mar;47(3):319–326. [PubMed] [Google Scholar]
  9. Gant N. F., Madden J. D., Siiteri P. K., MacDonald P. C. The metabolic clearance rate of dehydroisoandrosterone sulfate. IV. Acute effects of induced hypertension, hypotension, and naturesis in normal and hypertensive pregnancies. Am J Obstet Gynecol. 1976 Jan 15;124(2):143–148. doi: 10.1016/s0002-9378(16)33290-2. [DOI] [PubMed] [Google Scholar]
  10. Gant N. F., Madden J. D., Siteri P. K., MacDonald P. C. The metabolic clearance rate of dehydroisoandrosterone sulfate. III. The effect of thiazide diuretics in normal and future pre-eclamptic pregnancies. Am J Obstet Gynecol. 1975 Sep 15;123(2):159–163. [PubMed] [Google Scholar]
  11. Killam A. P., Rosenfeld C. R., Battaglia F. C., Makowski E. L., Meschia G. Effect of estrogens on the uterine blood flow of oophorectomized ewes. Am J Obstet Gynecol. 1973 Apr 15;115(8):1045–1052. doi: 10.1016/0002-9378(73)90552-8. [DOI] [PubMed] [Google Scholar]
  12. Ladner C., Brinkman C. R., 3rd, Weston P., Assali N. S. Dynamics of uterine circulation in pregnant and nonpregnant sheep. Am J Physiol. 1970 Jan;218(1):257–263. doi: 10.1152/ajplegacy.1970.218.1.257. [DOI] [PubMed] [Google Scholar]
  13. Lieb S. M., Cabalum T., Zugaib M., Erkkola R., Tabsh K., Ushioda E., Nuwayhid B. S., Brinkman C. R., 3rd, Assali N. S. Vascular reactivity to angiotensin II in the normotensive and hypertensive pregnant ewe. Am J Physiol. 1980 Feb;238(2):H209–H213. doi: 10.1152/ajpheart.1980.238.2.H209. [DOI] [PubMed] [Google Scholar]
  14. Lippert T. H., Cloeren S. E., Fridrich R. Assessment of uteroplacental hemodynamics in complicated pregnancy. Int J Gynaecol Obstet. 1978;16(4):274–280. doi: 10.1002/j.1879-3479.1979.tb00444.x. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Rosenfeld C. R., Killam A. P., Battaglia F. C., Makowski E. L., Meschia G. Effect of estradiol-17, on the magnitude and distribution of uterine blood flow in nonpregnant, oophorectomized ewes. Pediatr Res. 1973 Mar;7(3):139–148. doi: 10.1203/00006450-197303000-00006. [DOI] [PubMed] [Google Scholar]
  18. Rosenfeld C. R., Morriss F. H., Jr, Makowski E. L., Meschia G., Battaglia F. C. Circulatory changes in the reproductive tissues of ewes during pregnancy. Gynecol Invest. 1974;5(5-6):252–268. doi: 10.1159/000301658. [DOI] [PubMed] [Google Scholar]
  19. Rosenfeld C. R., West J. Circulatory response to systemic infusion of norepinephrine in the pregnant ewe. Am J Obstet Gynecol. 1977 Feb 15;127(4):376–383. doi: 10.1016/0002-9378(77)90493-8. [DOI] [PubMed] [Google Scholar]
  20. Shoemaker E. S., Gant N. F., Madden J. D., MacDonald P. C. The effect of thiazide diuretics on placental function. Tex Med. 1973 Oct;69(10):109–115. [PubMed] [Google Scholar]
  21. Speroff L., Haning R. V., Jr, Levin R. M. The effect of angiotensin II and indomethacin on uterine artery blood flow in pregnant monkeys. Obstet Gynecol. 1977 Nov;50(5):611–614. [PubMed] [Google Scholar]
  22. Terragno N. A., Terragno A., McGiff J. C. Prostaglandin E - angiotensin II interactions in the gravid uterus. Acta Physiol Lat Am. 1974;24(5):550–554. [PubMed] [Google Scholar]
  23. 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]

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

RESOURCES