Abstract
Vascular refractoriness to the systemic pressor effects of angiotension II (AII) develops normally during human pregnancy. To ascertain if the ewe might provide a suitable animal model to study the mechanisms responsible for this response (unique to pregnancy) we studied this phenomenon in unanesthetized, chronically instrumented nonpregnant and pregnant sheep, 68-143 d gestation. In these studies dose-response curves were established for changes in both mean arterial pressure and uterine blood flow. The pressor response to continuous infusions of AII increases as a function of the dose of AII in both nonpregnant and pregnant animals (P less than 0.001), R = 0.943 and 0.879, respectively. However, the pregnant animals were refractory to the pressor effects of AII, requiring 0.016 microgram of AII/min per kg to elicit a 20 mm HG rise in mean arterial pressure, in contrast to 0.009 for nonpregnant animals. The slope and intercept for the regression lines are different at P less than 0.001. In pregnant animals the dose-response curve for uterine blood flow was also determined. Increases in uterine blood flow were observed at doses of AII less than 0.016 microgram/min per kg, while larger doses resulted in a progressively greater reduction in blood flow. It appears likely that the ewe may serve as an animal model suitable for the further study of the unique pregnancy-modified systemic and uteroplacental vascular responses elicited by AII.
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- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Everett R. B., Worley R. J., MacDonald P. C., Gant N. F. Modification of vascular responsiveness to angiotensin II in pregnant women by intravenously infused 5alpha-dihydroprogesterone. Am J Obstet Gynecol. 1978 Jun 15;131(4):352–357. doi: 10.1016/0002-9378(78)90407-6. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- 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]
- Rosenfeld C. R., Barton M. D., Meschia G. Effects of epinephrine on distribution of blood flow in the pregnant ewe. Am J Obstet Gynecol. 1976 Jan 15;124(2):156–163. doi: 10.1016/s0002-9378(16)33292-6. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Talledo O. E. Renin-angiotensin system in normal and toxemic pregnancies. I. Angiotensin infusion test. Am J Obstet Gynecol. 1966 Sep 1;96(1):141–143. doi: 10.1016/s0002-9378(16)34655-5. [DOI] [PubMed] [Google Scholar]
- 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]