Abstract
Using a rat model, we investigated the effects of circulating factors in pregnancy on cerebrovascular and systemic vascular function by comparing myogenic reactivity, tone, and endothelial vasodilator production of the posterior cerebral artery (PCA) and mesenteric artery (MA) of nonpregnant (NP) animals perfused with nonpregnant and pregnant human plasma. Arteries from late pregnant (LP) animals were then perfused similarly to evaluate a potential adaptive effect of pregnancy on vessel function. A 3-hour exposure to pregnant plasma caused increased myogenic reactivity and tone in vessels from NP animals and produced a decreased endothelium-derived hyperpolarizing factor response in NP PCAs, findings that were not seen with MAs. The increased reactivity and tone noted in NP vessels was abolished when pregnant plasma was perfused through LP arteries, suggesting these vessels adapt during pregnancy to the vasoconstricting influence of pregnant plasma.
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Gerber RT, Anwar MA, Poston L. Enhanced acetylcholine induced relaxation in small mesenteric arteries from pregnant rats: an important role for endothelium-derived hyperpolarizing factor (EDHF). Br J Pharmacol. 1998;125(3):455–460.
Cipolla MJ, Binder ND, Osol G. Myoendometrial vs. placental uterine arteries: structural, mechanical, and functional differences in late-pregnant rabbits. Am J Obstet Gynecol. 1997; 177(1):215–221.
Davison JM, Dunlop W. Renal hemodynamics and tubular function normal human pregnancy. Kidney Int. 1980;18(2): 152–161.
Edouard DA, Pannier BM, London GM, Cuche JL, Safar ME. Venous and arterial behavior during normal pregnancy. Am J Physiol. 1998;274(5 pt 2):H1605-H1612.
Weiner CP, Thompson LP. Nitric oxide and pregnancy. Semin Perinatol. 1997;21(5):367–380.
Elsheikh A, Creatsas G, Mastorakos G, Milingos S, Loutradis D, Michalas S. The renin-aldosterone system during normal and hypertensive pregnancy. Arch Gynecol Obstet. 2001;264(4):182–185.
Gant NF, Worley RJ, Everett RB, MacDonald PC. Control of vascular responsiveness during human pregnancy. Kidney Int. 1980;18(2):253–258.
Gant NF, Daley GL, Chand S, Whalley PJ, MacDonald PC. A study of angiotensin II pressor response throughout primigravid pregnancy. J Clin Invest. 1973;52(11):2682–2689.
Magness RR, Cox K, Rosenfeld CR, Gant NF. Angiotensin II metabolic clearance rate and pressor responses in nonpregnant and pregnant women. Am J Obstet Gynecol. 1994;171(3): 668–679.
Talledo OE. Renin-angiotensin system in normal and toxemic pregnancies. I. Angiotensin infusion test. Am J Obstet Gynecol. 1966;96(1):141–143.
Massani ZM, Sanguinetti R, Gallegos R, Raimondi D. Angiotensin blood levels in normal and toxemic pregnancies. Am J Obstet Gynecol. 1967;99(3):313–317.
Cipolla MJ, Vitullo L, McKinnon J. Cerebral artery reactivity changes during pregnancy and the postpartum period: a role in eclampsia? Am J Physiol Heart Circ Physiol. 2004;286(6): H2127-H2132.
Cipolla MJ. Cerebrovascular function in pregnancy and eclampsia. Hypertension. 2007;50(1):14–24.
Gillham JC, Kenny LC, Baker PN. An overview of endothelium-derived hyperpolarising factor (EDHF) in normal and compromised pregnancies. Eur J Obstet Gynecol Reprod Biol. 2003;109(1):2–7.
Félétou M, Vanhoutte PM. Endothelium-dependent hyper-polarizations: past beliefs and present facts. Ann Med. 2007; 39(7):495–516.
Cipolla MJ, Smith J, Kohlmeyer MM, Godfrey JA. SKCa and IKCa Channels, myogenic tone, and vasodilator responses in middle cerebral arteries and parenchymal arterioles: effect of ischemia and reperfusion. Stroke. 2009;40(4):1451–1457.
Walsh SW. Eicosanoids in preeclampsia. Prostaglandins Leukot Essent Fatty Acids. 2004;70(2):223–232.
Ylikorkala O, Viinikka L. Thromboxane A2 in pregnancy and puerperium. Br Med J. 1980;281(6255):1601–1602.
Walsh SW. Preeclampsia: an imbalance in placental prostacyclin and thromboxane production. Am J Obstet Gynecol. 1985;152(3):335–340.
Khedun SM, Naicker T, Moodley J. Endothelin-1 activity in pregnancy. J Obstet Gynaecol. 2002;22(6):590–593.
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. 1990;71(6):1675–1677.
Timmermans PB, Wong PC, Chiu AT, et al. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev. 1993;45(2):205–251.
Gallinat S, Busche S, Raizada MK, Sumners C. The angiotensin II type 2 receptor: an enigma with multiple variations. Am J Physiol Endocrinol Metab. 2000;278(3):E357-E374.
Hanssens M, Keirse MJ, Spitz B, van Assche FA. Angiotensin II levels in hypertensive and normotensive pregnancies. Br J Obstet Gynaecol. 1991;98(2):155–161.
Vincent JM, Kwan YW, Chan SL, Perrin-Sarrado C, Atkinson J, Chillon JM. Constrictor and dilator effects of angiotensin II on cerebral arterioles. Stroke. 2005;36(12): 2691–2695.
Näveri L, Strömberg C, Saavedra JM. Angiotensin II AT1 receptor mediated contraction of the perfused rat cerebral artery. Neuroreport. 1994;5(17):2278–2280.
De Silva TM, Broughton BR, Drummond GR, Sobey CG, Miller AA. Gender influences cerebral vascular responses to angiotensin II through Nox2-derived reactive oxygen species. Stroke. 2009;40(4):1091–1097.
Faraci FM, Lamping KG, Modrick ML, Ryan MJ, Sigmund CD, Didion SP. Cerebral vascular effects of angiotensin II: new insights from genetic models. J Cereb Blood Flow Metab. 2006;26(4):449–455.
Stennett AK, Qiao X, Falone AE, Koledova VV, Khalil RA. Increased vascular angiotensin type 2 receptor expression and NOS-mediated mechanisms of vascular relaxation in pregnant rats. Am J Physiol Heart Circ Physiol. 2009;296(3):H745-H755.
Haberl RL, Anneser F, Villringer A, Einhaupl KM. Angiotensin II induces endothelium-dependent vasodilation of rat cerebral arterioles. Am J Physiol. 1990;258(6 pt 2):H1840-H1846.
Gwathmey TM, Shaltout HA, Pendergrass KD, et al. Nuclear angiotensin II type 2 (AT2) receptors are functionally linked to nitric oxide production. Am J Physiol Renal Physiol. 2009;296(6):F1484-F1493.
Grady EF, Sechi LA, Griffin CA, Schambelan M, Kalinyak JE. Expression of AT2 receptors in the developing rat fetus. J Clin Invest. 1991;88(3):921–933.
Judson JP, Nadarajah VD, Bong YC, Subramaniam K, Sivalingam N. A preliminary finding: immunohistochemical localisation and distribution of placental angiotensin II receptor subtypes in normal and preeclamptic pregnancies. Med J Malaysia. 2006;61(2):173–180.
Nickenig G, Baumer AT, Grohe C, et al. Estrogen modulates AT1 receptor gene expression in vitro and in vivo. Circulation. 1998;97(22):2197–2201.
Silva-Antonialli MM, Tostes RC, Fernandes L, et al. A lower ratio of AT1/AT2 receptors of angiotensin II is found in female than in male spontaneously hypertensive rats. Cardiovasc Res. 2004;62(3):587–593.
Faraci FM, Mayhan WG, Heistad DD. Segmental vascular responses to acute hypertension in cerebrum and brain stem. Am J Physiol. 1987;252(4 pt 2):H738-H742.
Baumbach GL, Heistad DD. Regional, segmental, and temporal heterogeneity of cerebral vascular autoregulation. Ann Biomed Eng. 1985;13(3–4):303–310.
Merchant SJ, Davidge ST. The role of matrix metalloproteinases in vascular function: implications for normal pregnancy and pre-eclampsia. BJOG. 2004;111(9):931–939.
Myers J, Irvine R, Gillham J, et al. Altered endothelial function in isolated human myometrial vessels induced by plasma from women with pre-eclampsia is not reproducible in isolated mouse vessels. Clin Sci (Lond). 2005;108(5):457–462.
Hayman R, Warren A, Brockelsby J, Johnson I, Baker P. Plasma from women with pre-eclampsia induces an in vitro alteration in the endothelium-dependent behaviour of myo-metrial resistance arteries. BJOG. 2000;107(1):108–115.
Hayman R, Warren A, Johnson I, Baker P. Inducible change in the behavior of resistance arteries from circulating factor in preeclampsia: an effect specific to myometrial vessels from pregnant women. Am J Obstet Gynecol. 2001;184(3):420–426.
Myers J, Mires G, Macleod M, Baker P. In preeclampsia, the circulating factors capable of altering in vitro endothelial function precede clinical disease. Hypertension. 2005;45(2):258–263.
Myers JE, Hart S, Armstrong S, et al. Evidence for multiple circulating factors in preeclampsia. Am J Obstet Gynecol. 2007;196(3):266.e1–266.e6.
Cipolla MJ, Bullinger LV, Godfrey JA. Pregnancy and PPARγ activation cause small vessel remodeling in the maternal brain and diminished cerebrovascular resistance: a role in eclampsia? Reprod Sci. 2009;16(3 suppl):91A–92A.
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Amburgey, Ö.A., Reeves, S.A., Bernstein, I.M. et al. Resistance Artery Adaptation to Pregnancy Counteracts the Vasoconstricting Influence of Plasma From Normal Pregnant Women. Reprod. Sci. 17, 29–39 (2010). https://doi.org/10.1177/1933719109345288
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DOI: https://doi.org/10.1177/1933719109345288