|
|
||||||||
AJP - Regulatory, Integrative and Comparative Physiology, Vol 272, Issue 2 441-R463, Copyright © 1997 by American Physiological Society
ARTICLES |
S. M. Sladek, R. R. Magness and K. P. Conrad
Magee-Womens Research Institute and Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pennsylvania 15213, USA.
This review will consider whether nitric oxide (NO) contributes to maternal systemic vasodilation during pregnancy, regulates uterine and fetoplacental blood flow, and is involved in uterine quiescence prior to parturition. Also, whether a deficiency of NO contributes to the hypertensive disorder of pregnancy, preeclampsia, will be considered. The biosynthesis of NO increases in gravid rats and sheep, but the status in normal human pregnancy and preeclampsia is controversial. NO contributes to maternal systemic vasodilation and reduced vascular reactivity during normal pregnancy; however, the relative contribution of NO is variable depending on the animal species, vascular bed, and vessel size. Impaired relaxation responses to acetylcholine, but not bradykinin or NO donors, are observed in small arteries from women with preeclampsia, suggesting a receptor or signal transduction defect, although NO may play little, if any, role here. Uterine arteries have increased endothelial nitric oxide synthase (NOS) activity, protein expression, and guanosine 3',5'-cyclic monophosphate production during pregnancy; however, whether these mediate uterine vasodilation during pregnancy remains to be established. NOS is expressed in the human placental syncytiotrophoblast and in the fetoplacental and umbilical vascular endothelium where basal production of NO contributes to low fetoplacental vascular resistance. Controversy exists over the status of placental NOS in preeclampsia, although an abnormality of umbilical NOS activity is likely. Finally, the uterus has NOS activity, which decreases at the end of gestation, and exogenous NO relaxes the myometrium, but whether endogenous NO contributes to uterine quiescence during pregnancy has yet to be confirmed.
This article has been cited by other articles:
![]() |
Y. Lu, H. Zhang, N. Gokina, M. Mandala, O. Sato, M. Ikebe, G. Osol, and S. A. Fisher Uterine artery myosin phosphatase isoform switching and increased sensitivity to SNP in a rat L-NAME model of hypertension of pregnancy Am J Physiol Cell Physiol, February 1, 2008; 294(2): C564 - C571. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. S. Gilbert, M. J. Ryan, B. B. LaMarca, M. Sedeek, S. R. Murphy, and J. P. Granger Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H541 - H550. [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] |
||||
![]() |
D. L. Daubert, D. Liu, I. H. Zucker, and V. L. Brooks Roles of nitric oxide and angiotensin II in the impaired baroreflex gain of pregnancy Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2179 - R2187. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. D. Mateo, G. Wu, F. W. Bazer, J. C. Park, I. Shinzato, and S. W. Kim Dietary L-Arginine Supplementation Enhances the Reproductive Performance of Gilts J. Nutr., March 1, 2007; 137(3): 652 - 656. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Xiao, J. N. Buchholz, and L. Zhang Pregnancy attenuates uterine artery pressure-dependent vascular tone: role of PKC/ERK pathway Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2337 - H2343. [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] |
||||
![]() |
C. R. Rosenfeld, T. Roy, K. DeSpain, and B. E. Cox Large-Conductance Ca2+-Dependent K+ Channels Regulate Basal Uteroplacental Blood Flow in Ovine Pregnancy Reproductive Sciences, September 1, 2005; 12(6): 402 - 408. [Abstract] [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] |
||||
![]() |
F.-X. Yi, R. R. Magness, and I. M. Bird Simultaneous imaging of [Ca2+]i and intracellular NO production in freshly isolated uterine artery endothelial cells: effects of ovarian cycle and pregnancy Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2005; 288(1): R140 - R148. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Xiao and L. Zhang Adaptation of uterine artery thick- and thin-filament regulatory pathways to pregnancy Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H142 - H148. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Kwon, S. P. Ford, F. W. Bazer, T. E. Spencer, P. W. Nathanielsz, M. J. Nijland, B. W. Hess, and G. Wu Maternal Nutrient Restriction Reduces Concentrations of Amino Acids and Polyamines in Ovine Maternal and Fetal Plasma and Fetal Fluids Biol Reprod, September 1, 2004; 71(3): 901 - 908. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. P. Conrad and J. Novak Emerging role of relaxin in renal and cardiovascular function Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2004; 287(2): R250 - R261. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Orshal and R. A. Khalil Interleukin-6 impairs endothelium-dependent NO-cGMP-mediated relaxation and enhances contraction in systemic vessels of pregnant rats Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2004; 286(6): R1013 - R1023. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Luksha, H. Nisell, and K. Kublickiene The mechanism of EDHF-mediated responses in subcutaneous small arteries from healthy pregnant women Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2004; 286(6): R1102 - R1109. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Xiao and L. Zhang Calcium Homeostasis and Contraction of the Uterine Artery: Effect of Pregnancy and Chronic Hypoxia Biol Reprod, April 1, 2004; 70(4): 1171 - 1177. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Kwon, G. Wu, C. J. Meininger, F. W. Bazer, and T. E. Spencer Developmental Changes in Nitric Oxide Synthesis in the Ovine Placenta Biol Reprod, March 1, 2004; 70(3): 679 - 686. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y.-L. Dong, S. Vegiraju, M. Chauhan, P. R. R. Gangula, G. D. V. Hankins, L. Goodrum, and C. Yallampalli Involvement of calcitonin gene-related peptide in control of human fetoplacental vascular tone Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H230 - H239. [Abstract] [Full Text] [PDF] |
||||
![]() |
M.-H. Wang, J. Wang, H.-H. Chang, B. A. Zand, M. Jiang, A. Nasjletti, and M. Laniado-Schwartzman Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats Am J Physiol Renal Physiol, August 1, 2003; 285(2): F295 - F302. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Xiao, X. Huang, W. J. Pearce, L. D. Longo, and L. Zhang Effect of cortisol on norepinephrine-mediated contractions in ovine uterine arteries Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1142 - H1151. [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] |
||||
![]() |
S. Veerareddy, C.-L. M. Cooke, P. N. Baker, and S. T. Davidge Vascular adaptations to pregnancy in mice: effects on myogenic tone Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2226 - H2233. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Nakatsuka, M. Takata, K. Tada, K. Asagiri, T. Habara, S. Noguchi, and T. Kudo A Long-term Transdermal Nitric Oxide Donor Improves Uteroplacental Circulation in Women With Preeclampsia J. Ultrasound Med., August 1, 2002; 21(8): 831 - 836. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. L. Brooks, K. A. Clow, and K. P. O'Hagan Pregnancy and acute baroreflex resetting in conscious rabbits Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2002; 283(2): R429 - R440. [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] |
||||
![]() |
J. M. Joyce, T. M. Phernetton, and R. R. Magness Effect of Uterine Blood Flow Occlusion on Shear Stress-Mediated Nitric Oxide Production and Endothelial Nitric Oxide Synthase Expression During Ovine Pregnancy Biol Reprod, July 1, 2002; 67(1): 320 - 326. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. B. Giardina, G. M. Green, K. L. Cockrell, J. P. Granger, and R. A. Khalil TNF-alpha enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R130 - R143. [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] |
||||
![]() |
T.M. Rahman and J. Wendon Severe hepatic dysfunction in pregnancy QJM, June 1, 2002; 95(6): 343 - 357. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Nakatsuka, M. Takata, K. Tada, and T. Kudo Effect of a Nitric Oxide Donor on the Ophthalmic Artery Flow Velocity Waveform in Preeclamptic Women J. Ultrasound Med., March 1, 2002; 21(3): 309 - 313. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. R. Davis, J. B. Giardina, G. M. Green, B. T. Alexander, J. P. Granger, and R. A. Khalil Reduced endothelial NO-cGMP vascular relaxation pathway during TNF-alpha -induced hypertension in pregnant rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2002; 282(2): R390 - R399. [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] |
||||
![]() |
B. T. Alexander, W. A. Bennett, R. A. Khalil, and J. P. Granger Preeclampsia: Linking Placental Ischemia with Cardiovascular-Renal Dysfunction Physiology, December 1, 2001; 16(6): 282 - 286. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. R. Abram, B. T. Alexander, W. A. Bennett, and J. P. Granger Role of neuronal nitric oxide synthase in mediating renal hemodynamic changes during pregnancy Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2001; 281(5): R1390 - R1393. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. L. Brooks, K. A. Clow, L. S. Welch, and G. D. Giraud Does nitric oxide contribute to the basal vasodilation of pregnancy in conscious rabbits? Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2001; 281(5): R1624 - R1632. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Lanlua, P.R.R. Gangula, G. Taglialatela, and C. Yallampalli Gestational Changes in Calcitonin Gene-Related Peptide, Nerve Growth Factor, and Its Receptors in Rat Dorsal Root Ganglia Biol Reprod, November 1, 2001; 65(5): 1601 - 1605. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. R. Rosenfeld Mechanisms regulating angiotensin II responsiveness by the uteroplacental circulation Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2001; 281(4): R1025 - R1040. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. P. Granger, B. T. Alexander, M. T. Llinas, W. A. Bennett, and R. A. Khalil Pathophysiology of Hypertension During Preeclampsia Linking Placental Ischemia With Endothelial Dysfunction Hypertension, September 1, 2001; 38(3): 718 - 722. [Abstract] [Full Text] |
||||
![]() |
L. A. Barron, J. B. Giardina, J. P. Granger, and R. A. Khalil High-Salt Diet Enhances Vascular Reactivity in Pregnant Rats With Normal and Reduced Uterine Perfusion Pressure Hypertension, September 1, 2001; 38(3): 730 - 735. [Abstract] [Full Text] |
||||
![]() |
A. P. Harris, S. Helou, C. A. Gleason, R. J. Traystman, and R. C. Koehler Fetal cerebral and peripheral circulatory responses to hypoxia after nitric oxide synthase inhibition Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2001; 281(2): R381 - R390. [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] |
||||
![]() |
C. R. Rosenfeld, D. N. Cornfield, and T. Roy Ca2+-activated K+ channels modulate basal and E2{beta}-induced rises in uterine blood flow in ovine pregnancy Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H422 - H431. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. J. Smolich NO supports right ventricular flow dominance and whole body O2 utilization in midgestation fetal lambs Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2001; 280(4): R1016 - R1022. [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] |
||||
![]() |
B. T. Alexander, S. E. Kassab, M. T. Miller, S. R. Abram, J. F. Reckelhoff, W. A. Bennett, and J. P. Granger Reduced Uterine Perfusion Pressure During Pregnancy in the Rat Is Associated With Increases in Arterial Pressure and Changes in Renal Nitric Oxide Hypertension, April 1, 2001; 37(4): 1191 - 1195. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Zhang, K. G. Stewart, and S. T. Davidge Endogenous estrogen mediates vascular reactivity and distensibility in pregnant rat mesenteric arteries Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H956 - H961. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Xiao, I. M. Bird, R. R. Magness, L. D. Longo, and L. Zhang Upregulation of eNOS in pregnant ovine uterine arteries by chronic hypoxia Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H812 - H820. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. G. Murphy, J. B. Fleming, K. L. Cockrell, J. P. Granger, and R. A. Khalil [Ca2+]i signaling in renal arterial smooth muscle cells of pregnant rat is enhanced during inhibition of NOS Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2001; 280(1): R87 - R99. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Kamada, M. Nakatsuka, K. Asagiri, S. Noguchi, T. Habara, M. Takata, and T. Kudo GnRH agonist-suppressed expression of nitric oxide synthases and generation of peroxynitrite in adenomyosis Hum. Reprod., December 1, 2000; 15(12): 2512 - 2519. [Abstract] [Full Text] [PDF] |
||||
![]() |
X.-B. Zhou, G.-X. Wang, P. Ruth, B. Huneke, and M. Korth BKCa channel activation by membrane-associated cGMP kinase may contribute to uterine quiescence in pregnancy Am J Physiol Cell Physiol, December 1, 2000; 279(6): C1751 - C1759. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. J. Kliman Uteroplacental Blood Flow : The Story of Decidualization, Menstruation, and Trophoblast Invasion Am. J. Pathol., December 1, 2000; 157(6): 1759 - 1768. [Full Text] [PDF] |
||||
![]() |
L. A. Danielson, L. J. Kercher, and K. P. Conrad Impact of gender and endothelin on renal vasodilation and hyperfiltration induced by relaxin in conscious rats Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2000; 279(4): R1298 - R1304. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Shah, A. Hobbs, R. Singh, J. Cuevas, L. J. Ignarro, and G. Chaudhuri Gastrointestinal motility during pregnancy: role of nitrergic component of NANC nerves Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2000; 279(4): R1478 - R1485. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. H. Nelson, O. S. Steinsland, Y. Wang, C. Yallampalli, Y.-L. Dong, and J. M. Sanchez Increased Nitric Oxide Synthase Activity and Expression in the Human Uterine Artery During Pregnancy Circ. Res., September 1, 2000; 87(5): 406 - 411. [Abstract] [Full Text] |
||||
![]() |
J. Bailey, C. Sparey, R. J. Phillips, K. Gilmore, S. C. Robson, W. Dunlop, and G.N. Europe-Finner Expression of the cyclic AMP-dependent transcription factors, CREB, CREM and ATF2, in the human myometrium during pregnancy and labour Mol. Hum. Reprod., July 1, 2000; 6(7): 648 - 660. [Abstract] [Full Text] [PDF] |
||||
![]() |
P.R.R. Gangula, S.J. Wimalawansa, and C. Yallampalli Pregnancy and sex steroid hormones enhance circulating calcitonin gene-related peptide concentrations in rats Hum. Reprod., April 1, 2000; 15(4): 949 - 953. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. A. Kanashiro, K. L. Cockrell, B. T. Alexander, J. P. Granger, and R. A. Khalil Pregnancy-associated reduction in vascular protein kinase C activity rebounds during inhibition of NO synthesis Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2000; 278(2): R295 - R303. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. K. Crews, J. N. Herrington, J. P. Granger, and R. |