Abstract
Uterine artery constrictor responses to elevation of intraluminal pressure (myogenic tone) are considerably enhanced in late pregnant rats, although the underlying causes remain unknown. A single uterine horn ligation model was used to differentiate local from systemic influences, and to test the hypothesis that factors associated with the site of placentation, rather than systemic hormonal changes, are primarily involved in the induction of this adaptive process. Radial uterine arteries were dissected from the gravid and non-gravid uterine horns of late pregnant rats, cannulated, and pressurized. Changes in arterial diameter and smooth muscle [Ca2+]i in response to the elevation of intraluminal pressure were studied using intact and endothelium-denuded arteries loaded with the ratiometric Ca2+-sensitive dye fura-2. Elevations of pressure from 10 to 60 and 100 mm Hg resulted in passive arterial distention of arteries from nongravid horns with a minor change in [Ca2+]i. In contrast, arteries from gravid horns developed myogenic tone associated with a significant elevation in [Ca2+]i. Synchronous oscillations in [Ca2+]i and lumen diameter were frequently observed in vessels from gravid horns. Endothelial denudation augmented tone in the gravid horn but did not uncover myogenic tone in vessels from the nongravid horn. In summary, pregnancy-associated uterine artery myogenic behavior is due to an upregulation of calcium-handling mechanisms, occurs independently of the endothelium, and is induced by local uteroplacental influences.
Similar content being viewed by others
References
Poston L, McCarthy AL, Ritter JM. Control of vascular resistance in the maternal and feto-placental arterial beds. Pharmacol Ther. 1995;65(2):215–239.
Sladek SM, Magness RR, Conrad KP. Nitric oxide and pregnancy. Am J Physiol Regul Integr Comp Physiol. 1997;272(2 pt 2):R441–R463.
Moll W. Structure adaptation and blood flow control in the uterine arterial system after hemochorial placentation. Eur J Obstet Gynecol Reprod Biol. 2003;110 Suppl 1:S19–S27.
Magness RR, Rosenfeld CR, Hassan A, Shaul PW. Endothelial vasodilator production by uterine and systemic arteries. I. Effects of ANG II on [PGI2] and NO in pregnancy. Am J Physiol Heart Circ Physiol. 1996;270(6 pt 2):H1914–H1923.
Bird IM, Zhang L, Magness RR. Possible mechanisms underlying pregnancy-induced changes in uterine artery endothelial function. Am J Physiol Regul Integr Comp Physiol. 2003;284(2): R245–R258.
Osol G, Cipolla M. Interaction of myogenic and adrenergic mechanisms in isolated, pressurized uterine radial arteries from late-pregnant and nonpregnant rats. Am J Obstet Gynecol. 1993;168(2):697–705.
D’Angelo G, Osol G. Regional variation in resistance artery diameter responses to alpha-adrenergic stimulation during pregnancy. Am J Physiol Heart Circ Physiol. 1993;264(1 pt2)H78–H85.
Xiao D, Pearce WJ, Zhang L. Pregnancy enhances endothelium-dependent relaxation of ovine uterine artery: role of NO and intracellular Ca2+. Am J Physiol Heart Circ Physiol. 2001;281(1):H183–H190. 9. Gokina NI, Goecks T. Upregulation of endothelial cell Ca2+ signaling contributes to pregnancy-enhanced vasodilation of rat uteroplacental arteries. Am J Physiol Heart Circ Physiol. 2006;290(5):H2124–H2135.
Gokina NI, Goecks T. Upregulation of endothelial cell Ca2+ signaling contributes to pregnancy-enhanced vasodilation of rat uteroplacental arteries. Am J Physiol Heart Circ Physiol. 2006;290(5):H2124–H2135
Veerareddy S, Cooke CL, Baker PN, Davidge ST. Vascular adaptations to pregnancy in mice: effects on myogenic tone. Am J Physiol Heart Circ Physiol. 2002;283(6):H2226–H2233.
Osol G, Mandala M. Maternal uterine vascular remodeling during pregnancy. Physiology (Bethesda). 2009;24:58–71.
Schubert R, Mulvany MJ. The myogenic response: established facts and attractive hypotheses. Clin Sci (Lond). 1999;96(4):313–326.
Davis MJ, Hill MA. Signaling mechanisms underlying the vascular myogenic response. Physiological Rev. 1999;79(2):387–423.
Hill MA, Zou H, Potocnik SJ, Meininger GA, Davis MJ. Invited review: arteriolar smooth muscle mechanotransduction: Ca2+ signaling pathways underlying myogenic reactivity. J Appl Physiol. 2001;91(2):973–983.
Osol G. Mechanotransduction by vascular smooth muscle. J Vasc Res. 1995;32(5):275–292.
Ledoux J, Werner ME, Brayden JE, Nelson MT. Calcium-activated potassium channels and the regulation of vascular tone. Physiology (Bethesda). 2006;21:69–78.
Brayden JE, Nelson MT. Regulation of arterial tone by activation of calcium-dependent potassium channels. Science. 1992;256(5056):532–535.
Cole WC, Chen TT, Clement-Chomienne O. Myogenic regulation of arterial diameter: role of potassium channels with a focus on delayed rectifier potassium current. Can J Physiol Pharmacol. 2005;83(8–9):755–765.
Osol G, Brekke JF, McElroy-Yaggy K, Gokina NI. Myogenic tone, reactivity, and forced dilatation: a three-phase model of in vitro arterial myogenic behavior. Am J Physiol Heart Circ Physiol. 2002;283(6):H2260–H2267.
Schubert R, Lidington D, Bolz SS. The emerging role of Ca2+ sensitivity regulation in promoting myogenic vasoconstriction. Cardiovasc Res. 2008;77(1):8–18.
Telezhkin V, Goecks T, Bonev AD, Osol G, Gokina NI. Decreased function of voltage-gated potassium channels contributes to augmented myogenic tone of uterine arteries in late pregnancy. Am J Physiol Heart Circ Physiol. 2008;294(1):H272–H284.
Novak J, Ramirez RJ, Gandley RE, Sherwood OD, Conrad KP. Myogenic reactivity is reduced in small renal arteries isolated from relaxin-treated rats. Am J Physiol Regul Integr Comp Physiol. 2002;283(2):R349–R355.
Meyer MC, Brayden JE, McLaughlin MK. Characteristics of vascular smooth muscle in the maternal resistance circulation during pregnancy in the rat. Am J Obstet Gynecol. 1993;169(6):1510–1516.
Gokina NI, Mandala M, Osol G. Induction of localized differences in rat uterine radial artery behavior and structure during gestation. Am J Obstet Gynecol. 2003;189(5): 1489–1493.
Hilgers RH, Bergaya S, Schiffers PM, et al. Uterine artery structural and functional changes during pregnancy in tissue kallikrein-deficient mice. Arterioscler Thromb Vasc Biol. 2003;23(10):1826–1832.
Veerareddy S, Campbell ME, Williams SJ, Baker PN, Davidge ST. Myogenic reactivity is enhanced in rat radial uterine arteries in a model of maternal undernutrition. Am J Obstet Gynecol. 2004;191(1):334–339.
Kublickiene KR, Cockell AP, Nisell H, Poston L. Role of nitric oxide in the regulation of vascular tone in pressurized and perfused resistance myometrial arteries from term pregnant women. Am J Obstet Gynecol. 1997;177(5):1263–1269.
Fuller R, Barron C, Mandala M, Gokina N, Osol G. Predominance of local over systemic factors in uterine arterial remodeling during pregnancy. Reprod Sci. 2009;16(5):489–500.
Annibale DJ, Rosenfeld CR, Stull JT, Kamm KE. Protein content and myosin light chain phosphorylation in uterine arteries during pregnancy. Am J Physiol Cell Physiol. 1990; 259(3 pt 1):C484–C489.
Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985;260(6):3440–3450.
Knot HJ, Nelson MT. Regulation of arterial diameter and wall [Ca2+] in cerebral arteries of rat by membrane potential and intravascular pressure. J Physiol. 1998;508(pt 1): 199–209.
Harder DR. Pressure-dependent membrane depolarization in cat middle cerebral artery. Circ Res. 1984;55(2):197–202.
Brekke JF, Gokina NI, Osol G. Vascular smooth muscle cell stress as a determinant of cerebral artery myogenic tone. Am J Physiol Heart Circ Physiol. 2002;283(6):H2210–H2216.
Ramsey EM, Chez RA, Doppman JL. Radioangiographic measurement of the internal diameters of the uteroplacental arteries in rhesus monkeys. Am J Obstet Gynecol. 1979;135(2):247–251.
Osol G, Cipolla M. Pregnancy-induced changes in the three-dimensional mechanical properties of pressurized rat uteroplacental (radial) arteries. Am J Obstet Gynecol. 1993;168(1 pt 1):268–274.
Berridge MJ. Calcium signalling and cell proliferation. Bioessays. 1995;17(6):491–500.
Mandegar M, Fung YC, Huang W, Remillard CV, Rubin LJ, Yuan JX. Cellular and molecular mechanisms of pulmonary vascular remodeling: role in the development of pulmonary hypertension. Microvasc Res. 2004;68(2):75–103.
Platoshyn O, Golovina VA, Bailey CL, et al. Sustained membrane depolarization and pulmonary artery smooth muscle cell proliferation. Am J Physiol Cell Physiol. 2000;279(5): C1540–C1549.
Berk BC. Vascular smooth muscle growth: autocrine growth mechanisms. Physiol Rev. 2001;81(3):999–1030.
Landsberg JW, Yuan JX. Calcium and TRP channels in pulmonary vascular smooth muscle cell proliferation. News Physiol Sci. 2004;19:44–50.
Cipolla MJ, Binder ND, Osol G. Myoendometrial versus placental uterine arteries: structural, mechanical, and functional differences in late-pregnant rabbits. Am J Obstet Gynecol. 1997;177(1):215–221.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gokina, N.I., Kuzina, O.Y., Fuller, R. et al. Local Uteroplacental Influences are Responsible for the Induction of Uterine Artery Myogenic Tone during Rat Pregnancy. Reprod. Sci. 16, 1072–1081 (2009). https://doi.org/10.1177/1933719109340927
Published:
Issue Date:
DOI: https://doi.org/10.1177/1933719109340927