| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Cardiovascular Kidney Institute and Division of Nephrology and Hypertension, Georgetown University, Washington, DC, USA
2 Division of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
* To whom correspondence should be addressed. E-mail: wilcoxch{at}georgetown.edu.
We investigated the hypothesis that thromboxane A2 (TxA2)- prostaglandin H2 receptors (TP-Rs) mediate the hemodynamic responses and increase in reactive oxygen species (ROS) to angiotensin II (AngII; 400ng.kg-1.min-1 s.c. for 14 days) in TP-R knockout (TP-/-) and wild (+/+) mice. TP-/- had normal basal mean arterial blood pressure (MAP) and glomerular filtration rate but reduced renal blood flow (RBF) and increased filtration fraction (FF) and renal vascular resistance (RVR) and markers ofROS (TBARS and 8-isoprostane PGF2
) and nitric oxide (NOx). Infusion of AngII into TP+/+ increased ROS and thromboxane B2 (TxB2), and increased RVR and FF. AngII infusion into TP-/- mice reduced angiotensin I and
increased aldosterone, but caused a blunted increase in MAP (TP-/-; +6±2 vs. TP+/+; +15±3mmHg) and failed to increase FF, ROS or TxB2, but
increased nitric oxide (NOx) and paradoxically decreased RVR (-2.1+1.7 vs.+2.6±0.8mmHg.ml-1.min-1.g-1). Blockade of AT1-receptor of TP-/- mice
infused with AngII reduced the MAP (-8mmHg) and aldosterone, but did not change the RVR or ROS.
In conclusion: during an AngII slow pressor response, AT1-receptors activate TP-Rs that generate ROS and prostaglandins but inhibit NO. TP-Rs mediate all of the increase in RVR and FF, part of the increase in MAP, but
are not implicated in the suppression of angiotensin I or increase in aldosterone. TP-/- mice have a basal increase in RVR and FF associated with ROS.
This article has been cited by other articles:
|
|
 |
|
  J. Xu and M.-H. Zou Molecular Insights and Therapeutic Targets for Diabetic Endothelial Dysfunction Circulation, September 29, 2009; 120(13): 1266 - 1286. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Francois, N. Makhanova, P. Ruiz, J. Ellison, L. Mao, H. A. Rockman, and T. M. Coffman A role for the thromboxane receptor in L-NAME hypertension Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1096 - F1102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Crowley, C. W. Frey, S. K. Gould, R. Griffiths, P. Ruiz, J. L. Burchette, D. N. Howell, N. Makhanova, M. Yan, H.-S. Kim, et al. Stimulation of lymphocyte responses by angiotensin II promotes kidney injury in hypertension Am J Physiol Renal Physiol, August 1, 2008; 295(2): F515 - F524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Thachil The implications of aspirin resistance in renal failure NDT Plus, June 1, 2008; 1(3): 192 - 193. [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Welch, K. Patel, P. Modlinger, M. Mendonca, N. Kawada, K. Dennehy, S. Aslam, and C. S. Wilcox Roles of vasoconstrictor prostaglandins, COX-1 and -2, and AT1, AT2, and TP receptors in a rat model of early 2K,1C hypertension Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2644 - H2649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. B. Vagnes, B. M. Iversen, and W. J. Arendshorst Short-term ANG II produces renal vasoconstriction independent of TP receptor activation and TxA2/isoprostane production Am J Physiol Renal Physiol, September 1, 2007; 293(3): F860 - F867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sebekova, T. Eifert, A. Klassen, A. Heidland, and K. Amann Renal Effects of S18886 (Terutroban), a TP Receptor Antagonist, in an Experimental Model of Type 2 Diabetes Diabetes, April 1, 2007; 56(4): 968 - 974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-L. Tain and C. Baylis Dissecting the Causes of Oxidative Stress in an In Vivo Model of Hypertension Hypertension, November 1, 2006; 48(5): 828 - 829. [Full Text] [PDF]
|
|
|
|
|
|
A. L. Opay, C. R. Mouton, J. J. Mullins, and K. D. Mitchell Cyclooxygenase-2 inhibition normalizes arterial blood pressure in CYP1A1-REN2 transgenic rats with inducible ANG II-dependent malignant hypertension Am J Physiol Renal Physiol, September 1, 2006; 291(3): F612 - F618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Qi, H. Cai, J. D. Morrow, and M. D. Breyer Differentiation of Cyclooxygenase 1- and 2-Derived Prostanoids in Mouse Kidney and Aorta Hypertension, August 1, 2006; 48(2): 323 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Wilcox Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension? Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R913 - R935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Imig, X. Zhao, C. Z. Zaharis, J. J. Olearczyk, D. M. Pollock, J. W. Newman, I.-H. Kim, T. Watanabe, and B. D. Hammock An Orally Active Epoxide Hydrolase Inhibitor Lowers Blood Pressure and Provides Renal Protection in Salt-Sensitive Hypertension Hypertension, October 1, 2005; 46(4): 975 - 981. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
