(Hypertension. 1999;33:435-439.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Differential Expression of Renal Nitric Oxide Synthase Isoforms During Pregnancy in Rats
Correspondence to Joey P. Granger, PhD, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216-4505. E-mail jgranger{at}physiology.umsmed.edu
Abstract—Alterations in nitric oxide (NO) production have been suggested to play a role in mediating changes in renal function during normal pregnancy and in pregnancy-induced hypertension. Although NO production is enhanced during normal pregnancy, the mechanisms for the increase are unknown. The purpose of this study was to determine whether the elevation in NO production during pregnancy is associated with increases in renal expression of endothelial (eNOS), inducible (iNOS), and neuronal (nNOS) nitric oxide synthases. To achieve this goal we examined systemic and renal hemodynamics, urinary excretion of nitrate/nitrite, and renal protein expression of the three NOS isoforms in prepregnant rats, pregnant rats at days 6, 13, and 19 of gestation and at day 4 postpartum. Mean arterial pressure decreased by 14% in late pregnancy whereas the glomerular filtration rate and renal plasma flow increased by 21% and 24%, respectively, in mid pregnancy. Excretion of nitrate/nitrite increased throughout pregnancy with a 3.4-fold increase present at day 19 (12.2±0.7 to 41.1±1.3 µmol/24 h). Renal eNOS protein expression decreased by 39% during pregnancy with the lowest level resulting at day 19 and returning to virgin levels by day 4 post partum. In contrast, renal iNOS and nNOS protein expression increased 31% and 25%, respectively, with highest expression occurring for both at day 13 of pregnancy. These data suggest that the increased NO production and renal hemodynamics associated with pregnancy in rats may be caused by the upregulation of iNOS and nNOS in the kidney.
Key Words: kidney • glomerular filtration rate • renal blood flow • endothelial factors
This article has been cited by other articles:
 |
|
 |
|
  A. K. Stennett, X. Qiao, A. E. Falone, V. V. Koledova, and R. A. Khalil Increased vascular angiotensin type 2 receptor expression and NOS-mediated mechanisms of vascular relaxation in pregnant rats Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H745 - H755. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Game, J. Allard, G. Escourrou, P. Gourdy, I. Tack, P. Rischmann, J.-F. Arnal, and B. Malavaud Estradiol increases urethral tone through the local inhibition of neuronal nitric oxide synthase expression Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R851 - R857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Stark, L. Dierkx, V. L. Clifton, and I. M. R. Wright Alterations in the Maternal Peripheral Microvascular Response in Pregnancies Complicated by Preeclampsia and the Impact of Fetal Sex Reproductive Sciences, December 1, 2006; 13(8): 573 - 578. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Huang, H.-H. Chang, Y. Xu, D. S. Reddy, J. Du, Y. Zhou, Z. Dong, J. R. Falck, and M.-H. Wang Epoxyeicosatrienoic Acid Inhibition Alters Renal Hemodynamics During Pregnancy Experimental Biology and Medicine, December 1, 2006; 231(11): 1744 - 1752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Huang, Y. Zhou, V. T. Raju, J. Du, H.-H. Chang, C.-Y. Wang, M. W. Brands, J. R. Falck, and M.-H. Wang Renal 20-HETE inhibition attenuates changes in renal hemodynamics induced by L-NAME treatment in pregnant rats Am J Physiol Renal Physiol, November 1, 2005; 289(5): F1116 - F1122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Kerchner, J. Novak, K. Hanley-Yanez, K. D. Doty, L. A. Danielson, and K. P. Conrad Evidence against the Hypothesis that Endothelial Endothelin B Receptor Expression Is Regulated by Relaxin and Pregnancy Endocrinology, June 1, 2005; 146(6): 2791 - 2797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Herrera and J. L. Garvin Recent Advances in the Regulation of Nitric Oxide in the Kidney Hypertension, June 1, 2005; 45(6): 1062 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhou, H.-H. Chang, J. Du, C.-Y. Wang, Z. Dong, and M.-H. Wang Renal epoxyeicosatrienoic acid synthesis during pregnancy Am J Physiol Renal Physiol, January 1, 2005; 288(1): F221 - F226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Cherla and E. A. Jaimes Role of L-Arginine in the Pathogenesis and Treatment of Renal Disease J. Nutr., October 1, 2004; 134(10): 2801S - 2806S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Novak, A. Rajakumar, T. M. Miles, and K. P. Conrad Nitric Oxide Synthase Isoforms in the Rat Kidney During Pregnancy Reproductive Sciences, July 1, 2004; 11(5): 280 - 288. [Abstract] [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]
|
|
|
|
|
|
B. T. Alexander, M. T. Llinas, W. C. Kruckeberg, and J. P. Granger L-Arginine Attenuates Hypertension in Pregnant Rats With Reduced Uterine Perfusion Pressure Hypertension, April 1, 2004; 43(4): 832 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Orshal and R. A. Khalil Reduced Endothelial NO-cGMP-Mediated Vascular Relaxation and Hypertension in IL-6-Infused Pregnant Rats Hypertension, February 1, 2004; 43(2): 434 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Sedeek, M. T. Llinas, H. Drummond, L. Fortepiani, S. R. Abram, B. T. Alexander, J. F. Reckelhoff, and J. P. Granger Role of Reactive Oxygen Species in Endothelin-Induced Hypertension Hypertension, October 1, 2003; 42(4): 806 - 810. [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]
|
|
|
|
|
|
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. P. Granger Maternal and fetal adaptations during pregnancy: lessons in regulatory and integrative physiology Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2002; 283(6): R1289 - R1292. [Full Text] [PDF]
|
|
|
|
|
|
A. Linke, W. Li, H. Huang, Z. Wang, and T. H. Hintze Role of cardiac eNOS expression during pregnancy in the coupling of myocardial oxygen consumption to cardiac work Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1208 - H1214. [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. 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]
|
|
|
|
|
|
M.-H. Wang, B. A. Zand, A. Nasjletti, and M. Laniado-Schwartzman Renal 20-hydroxyeicosatetraenoic acid synthesis during pregnancy Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2002; 282(2): R383 - R389. [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]
|
|
|
|
|
|
B. T. Alexander, K. Cockrell, F. D. Cline, and J. P. Granger Inducible Nitric Oxide Synthase Inhibition Attenuates Renal Hemodynamics During Pregnancy Hypertension, February 1, 2002; 39(2): 586 - 590. [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]
|
|
|
|
|
|
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] [PDF]
|
|
|
|
|
|
M. A. Cadnapaphornchai, M. Ohara, K. G. Morris Jr., M. Knotek, B. Rogachev, T. Ladtkow, E. P. Carter, and R. W. Schrier Chronic NOS inhibition reverses systemic vasodilation and glomerular hyperfiltration in pregnancy Am J Physiol Renal Physiol, April 1, 2001; 280(4): F592 - F598. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
C. A. Kanashiro, B. T. Alexander, J. P. Granger, and R. A. Khalil Ca2+-Insensitive Vascular Protein Kinase C During Pregnancy and NOS Inhibition Hypertension, October 1, 1999; 34(4): 924 - 930. [Abstract] [Full Text] [PDF]
|
|