© 2000 American Heart Association, Inc.
Integrative Physiology |
Increased Nitric Oxide Synthase Activity and Expression in the Human Uterine Artery During Pregnancy
From the Departments of Anesthesiology (S.H.N., Y.W., J.M.S.), Pharmacology and Toxicology (O.S.S.), and Obstetrics and Gynecology (C.Y., Y.-L.D.), University of Texas Medical Branch, Galveston, Tex.
Correspondence to Dr Sharon H. Nelson, Department of Anesthesiology, Route 0591, University of Texas Medical Branch, Galveston, TX 77555. E-mail snelson{at}utmb.edu
Abstract—Evidence exists that NO plays a role in the vasodilation that occurs during pregnancy. The purpose of the present study was to determine whether the role of NO is associated with an increase in the activity and protein expression of NO synthase (NOS) in the human uterine artery. Uterine arteries were obtained from pregnant patients (P arteries) and nonpregnant patients (NP arteries). NOS activity was estimated with the L-[3H]-arginine–to–L-[3H]-citrulline conversion method and on the basis of changes in tissue levels of cGMP. Western immunoblotting and immunohistochemistry were used to assess NOS protein expression. Ca2+-dependent NOS activity was 8 times greater (P<0.01) in P than in NP arteries. Although most of this pregnancy-induced increase in NOS activity was Ca2+ dependent (64%), a considerable portion was Ca2+ independent. Expressions of endothelial NOS (eNOS) and neuronal NOS, but not inducible NOS, were demonstrated in P and NP arteries. The eNOS was located in the endothelium and stained with a qualitative order of P arteries>NP arteries (follicular)>NP arteries (luteal). The neuronal NOS was located in the adventitia of P and NP arteries. Basal NO-dependent and bradykinin-stimulated levels of cGMP were higher (P<0.05) in P than in NP arteries. These results indicate that an upregulation of eNOS protein expression could account for the increased NO synthesis/release in the human uterine artery during pregnancy.
Key Words: cyclic GMP • bradykinin • immunohistochemistry • N
-nitro-L-arginine methyl ester • Ca2+ • nitric oxide synthase
This article has been cited by other articles:
 |
|
 |
|
  C. Wedel Jones, M. Mandala, C. Barron, I. Bernstein, and G. Osol Mechanisms Underlying Maternal Venous Adaptation in Pregnancy Reproductive Sciences, June 1, 2009; 16(6): 596 - 604. [Abstract] [PDF]
|
|
|
|
 |
|
 G. Osol and M. Mandala Maternal Uterine Vascular Remodeling During Pregnancy Physiology, February 1, 2009; 24(1): 58 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zhang, D. Xiao, and X. Hu Effect of cGMP on Pharmacomechanical Coupling in the Uterine Artery of Near-Term Pregnant Sheep J. Pharmacol. Exp. Ther., November 1, 2008; 327(2): 425 - 431. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Meziani, A. Tesse, S. Welsch, H. Kremer, M. Barthelmebs, R. Andriantsitohaina, F. Schneider, and A. Gairard Expression and Biological Activity of Parathyroid Hormone-Related Peptide in Pregnant Rat Uterine Artery: Any Role for 8-Iso-Prostaglandin F2{alpha}? Endocrinology, February 1, 2008; 149(2): 626 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Telezhkin, T. Goecks, A. D. Bonev, G. Osol, and N. I. Gokina Decreased function of voltage-gated potassium channels contributes to augmented myogenic tone of uterine arteries in late pregnancy Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H272 - H284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-A. Scott, A. Tremblay, M. Brochu, and J. St-Louis Vasorelaxant action of 17 -estradiol in rat uterine arteries: role of nitric oxide synthases and estrogen receptors Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3713 - H3719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xiao, X. Huang, S. Yang, and L. Zhang Direct Effects of Nicotine on Contractility of the Uterine Artery in Pregnancy J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 180 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tesse, F. Meziani, E. David, N. Carusio, H. Kremer, F. Schneider, and R. Andriantsitohaina Microparticles from preeclamptic women induce vascular hyporeactivity in vessels from pregnant mice through an overproduction of NO Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H520 - H525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xiao, X. Huang, L. D. Longo, W. J. Pearce, and L. Zhang Regulation of baseline Ca2+ sensitivity in permeabilized uterine arteries: effect of pregnancy Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H413 - H420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Guo, X. Lu, H. Ren, E. R. Levin, and G. S. Kassab Estrogen modulates the mechanical homeostasis of mouse arterial vessels through nitric oxide Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1788 - H1797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. I. Gokina and T. Goecks Upregulation of endothelial cell Ca2+ signaling contributes to pregnancy-enhanced vasodilation of rat uteroplacental arteries Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H2124 - H2135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Nesbitt, R. J. Murphy, and K. P. O'Hagan Effect of gestational stage on uterine artery blood flow during exercise in rabbits J Appl Physiol, December 1, 2005; 99(6): 2159 - 2165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Vonnahme, M. E. Wilson, Y. Li, H. L. Rupnow, T. M. Phernetton, S. P. Ford, and R. R. Magness Circulating levels of nitric oxide and vascular endothelial growth factor throughout ovine pregnancy J. Physiol., May 15, 2005; 565(1): 101 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H.P. Hilgers, S. Bergaya, P. M.H. Schiffers, P. Meneton, C. M. Boulanger, D. Henrion, B. I. Levy, and J. G.R. De Mey Uterine Artery Structural and Functional Changes During Pregnancy in Tissue Kallikrein-Deficient Mice Arterioscler Thromb Vasc Biol, October 1, 2003; 23(10): 1826 - 1832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.A. Kelly, B.C. Bond, and L. Poston Gestational profile of matrix metalloproteinases in rat uterine artery Mol. Hum. Reprod., June 1, 2003; 9(6): 351 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Toda and T. Okamura The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels Pharmacol. Rev., June 1, 2003; 55(2): 271 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Rosenfeld, C. Chen, T. Roy, and X.-T. Liu Estrogen Selectively Up-Regulates eNOS and nNOS in Reproductive Arteries By Transcriptional Mechanisms Reproductive Sciences, May 1, 2003; 10(4): 205 - 215. [Abstract] [PDF]
|
|
|
|
|
|
S. Mateev, A. H. Sillau, R. Mouser, R. E. McCullough, M. M. White, D. A. Young, and L. G. Moore Chronic hypoxia opposes pregnancy-induced increase in uterine artery vasodilator response to flow Am J Physiol Heart Circ Physiol, March 1, 2003; 284(3): H820 - H829. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. M. Bird, L. Zhang, and R. R. Magness Possible mechanisms underlying pregnancy-induced changes in uterine artery endothelial function Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2003; 284(2): R245 - R258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Murphy, J. N. Herrington, J. P. Granger, and R. A. Khalil Enhanced [Ca2+]i in renal arterial smooth muscle cells of pregnant rats with reduced uterine perfusion pressure Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H393 - H403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Sullivan, A. D. Giulumian, D. M. Pollock, L. C. Fuchs, and J. S. Pollock Functional NOS 1 in the rat mesenteric arterial bed Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H658 - H663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Khalil and J. P. Granger Vascular mechanisms of increased arterial pressure in preeclampsia: lessons from animal models Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R29 - R45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xiao, X. Huang, S. Bae, C. A. Ducsay, and L. Zhang Cortisol-mediated potentiation of uterine artery contractility: effect of pregnancy Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H238 - H246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Joyce, T. M. Phernetton, C. E. Shaw, M. L. Modrick, and R. R. Magness Endothelial vasodilator production by uterine and systemic arteries. IX. eNOS gradients in cycling and pregnant ewes Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H342 - H348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. Buhimschi, G. Hall, L. P. Thompson, and C. P. Weiner Pregnancy and estradiol decrease GTPase activity in the guinea pig uterine artery Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H2168 - H2175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xiao, W. J. Pearce, and L. Zhang Pregnancy enhances endothelium-dependent relaxation of ovine uterine artery: role of NO and intracellular Ca2+ Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H183 - H190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Magness, J. A. Sullivan, Y. Li, T. M. Phernetton, and I. M. Bird Endothelial vasodilator production by uterine and systemic arteries. VI. Ovarian and pregnancy effects on eNOS and NOx Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1692 - H1698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Rupnow, T. M. Phernetton, C. E. Shaw, M. L. Modrick, I. M. Bird, and R. R. Magness Endothelial vasodilator production by uterine and systemic arteries. VII. Estrogen and progesterone effects on eNOS Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1699 - H1705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. M. Miller Vascular Control During Pregnancy : Extending Experimental Findings to Humans Circ. Res., September 1, 2000; 87(5): 344 - 345. [Full Text] [PDF]
|
|