(Hypertension. 2000;36:276.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Renal Changes Induced by a Cyclooxygenase-2 Inhibitor During Normal and Low Sodium Intake
From the Departamento de Fisiología (F.R., M.T.L., J.D.G., F.J.S.), Facultad de Medicina, Murcia, Spain; and the Unidad de Hematología y Oncología Clínica (J.R.), Centro Regional de Hemodonación, Murcia, Spain.
Correspondence to Dr F. Javier Salazar, Departamento de Fisiología, Facultad de Medicina, 30100 Murcia, Spain. E-mail salazar{at}fcu.um.es
Abstract—Cyclooxygenase-2 (COX-2) has been identified in renal tissues under normal conditions, with its expression enhanced during sodium restriction. To evaluate the role of COX-2–derived metabolites in the regulation of renal function, we infused a selective inhibitor (nimesulide) in anesthetized dogs with normal or low sodium intake. The renal effects elicited by nimesulide and a non–isozyme-specific inhibitor (meclofenamate) were compared during normal sodium intake. In ex vivo assays, meclofenamate, but not nimesulide, prevented the platelet aggregation elicited by arachidonic acid. During normal sodium intake, nimesulide infusion (n=6) had no effects on arterial pressure or renal hemodynamics but did reduce urinary sodium excretion, urine flow rate, and fractional lithium excretion. In contrast, nimesulide administration increased arterial pressure and decreased renal blood flow, urine flow rate, and fractional lithium excretion during low sodium intake (n=6). COX-2 inhibition reduced urinary prostaglandin E2 excretion in both groups but did not modify plasma renin activity in dogs with low (8.1±1.1 ng angiotensin I · mL-1 · h-1) or normal (1.8±0.4 ng angiotensin I · mL-1 · h-1) sodium intake. Meclofenamate infusion in dogs with normal sodium intake (n=8) induced a greater renal hemodynamic effect than nimesulide infusion. These results suggest that COX-2–derived metabolites (1) are involved in the regulation of sodium excretion in dogs with normal sodium intake, (2) play an important role in the regulation of renal hemodynamic and excretory function in dogs with low sodium intake, and (3) are not involved in the maintenance of the high renin levels during a long-term decrease in sodium intake.
Key Words: renal circulation • kidney • cyclooxygenase • sodium • renin • prostaglandins
This article has been cited by other articles:
 |
|
 |
|
  B. Yao, R. C. Harris, and M.-Z. Zhang Intrarenal Dopamine Attenuates Deoxycorticosterone Acetate/High Salt-Induced Blood Pressure Elevation in Part Through Activation of a Medullary Cyclooxygenase 2 Pathway Hypertension, November 1, 2009; 54(5): 1077 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Y.-C. Peng, D. Sankaran, M. R. Ogborn, and H. M. Aukema Dietary Soy Protein Selectively Reduces Renal Prostanoids and Cyclooxygenases in Polycystic Kidney Disease Experimental Biology and Medicine, July 1, 2009; 234(7): 737 - 743. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. A. Radi Pathophysiology of Cyclooxygenase Inhibition in Animal Models Toxicol Pathol, January 1, 2009; 37(1): 34 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Salazar, V. Reverte, F. Saez, A. Loria, M. T. Llinas, and F. J. Salazar Age- and Sodium-Sensitive Hypertension and Sex-Dependent Renal Changes in Rats With a Reduced Nephron Number Hypertension, April 1, 2008; 51(4): 1184 - 1189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Z.I. Cherney, J. A. Miller, J. W. Scholey, T. J. Bradley, C. Slorach, J. R. Curtis, M. G. Dekker, R. Nasrallah, R. L. Hebert, and E. B. Sochett The Effect of Cyclooxygenase-2 Inhibition on Renal Hemodynamic Function in Humans With Type 1 Diabetes Diabetes, March 1, 2008; 57(3): 688 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Patterson, J. J. Mullins, and K. D. Mitchell Renoprotective effects of neuronal NOS-derived nitric oxide and cyclooxygenase-2 metabolites in transgenic rats with inducible malignant hypertension Am J Physiol Renal Physiol, January 1, 2008; 294(1): F205 - F211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Loria, V. Reverte, F. Salazar, F. Saez, M. T. Llinas, and F. J. Salazar Sex and age differences of renal function in rats with reduced ANG II activity during the nephrogenic period Am J Physiol Renal Physiol, August 1, 2007; 293(2): F506 - F510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Matzdorf, A. Kurtz, and K. Hocherl COX-2 activity determines the level of renin expression but is dispensable for acute upregulation of renin expression in rat kidneys Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1782 - F1790. [Abstract] [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]
|
|
|
|
|
|
H. I. Abdullah, P. L. Pedraza, S. Hao, K. D. Rodland, J. C. McGiff, and N. R. Ferreri NFAT regulates calcium-sensing receptor-mediated TNF production Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1110 - F1117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Warford-Woolgar, C. Y.-C. Peng, J. Shuhyta, A. Wakefield, D. Sankaran, M. Ogborn, and H. M. Aukema Selectivity of cyclooxygenase isoform activity and prostanoid production in normal and diseased Han:SPRD-cy rat kidneys Am J Physiol Renal Physiol, April 1, 2006; 290(4): F897 - F904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Harris and M. D. Breyer Update on Cyclooxygenase-2 Inhibitors Clin. J. Am. Soc. Nephrol., March 1, 2006; 1(2): 236 - 245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yang, Y. G. Huang, W. Ye, P. Hansen, J. B. Schnermann, and J. P. Briggs Influence of genetic background and gender on hypertension and renal failure in COX-2-deficient mice Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1125 - F1132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Zewde and D. L. Mattson Inhibition of Cyclooxygenase-2 in the Rat Renal Medulla Leads to Sodium-Sensitive Hypertension Hypertension, October 1, 2004; 44(4): 424 - 428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-F. Cheng and R. C. Harris Cyclooxygenases, the Kidney, and Hypertension Hypertension, March 1, 2004; 43(3): 525 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Castrop, J. Klar, C. Wagner, K. Hocherl, and A. Kurtz General inhibition of renocortical cyclooxygenase-2 expression by the renin-angiotensin system Am J Physiol Renal Physiol, March 1, 2003; 284(3): F518 - F524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Lopez, M. T. Llinas, F. Roig, and F. J. Salazar Role of nitric oxide and cyclooxygenase-2 in regulating the renal hemodynamic response to norepinephrine Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2003; 284(2): R488 - R493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Roig, M. T. Llinas, R. Lopez, and F. J. Salazar Role of Cyclooxygenase-2 in the Prolonged Regulation of Renal Function Hypertension, November 1, 2002; 40(5): 721 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hocherl, F. Dreher, H. Vitzthum, J. Kohler, and A. Kurtz Cyclosporine A Suppresses Cyclooxygenase-2 Expression in the Rat Kidney J. Am. Soc. Nephrol., October 1, 2002; 13(10): 2427 - 2436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-F. Cheng, S.-W. Wang, M.-Z. Zhang, J. A. McKanna, R. Breyer, and R. C. Harris Prostaglandins that increase renin production in response to ACE inhibition are not derived from cyclooxygenase-1 Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2002; 283(3): R638 - R646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hocherl, M. C. Kammerl, K. Schumacher, D. Endemann, H. F. Grobecker, and A. Kurtz Role of prostanoids in regulation of the renin-angiotensin-aldosterone system by salt intake Am J Physiol Renal Physiol, August 1, 2002; 283(2): F294 - F301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. McCrory and S. G. E. Lindahl Cyclooxygenase Inhibition for Postoperative Analgesia Anesth. Analg., July 1, 2002; 95(1): 169 - 176. [Full Text] [PDF]
|
|
|
|
|
|
W. H. Beierwaltes Cyclooxygenase-2 products compensate for inhibition of nitric oxide regulation of renal perfusion Am J Physiol Renal Physiol, July 1, 2002; 283(1): F68 - F72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Kammerl, W. Richthammer, A. Kurtz, and B. K. Kramer Angiotensin II feedback is a regulator of renocortical renin, COX-2, and nNOS expression Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1613 - R1617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Llinas, R. Lopez, F. Rodriguez, F. Roig, and F. J. Salazar Role of COX-2-derived metabolites in regulation of the renal hemodynamic response to norepinephrine Am J Physiol Renal Physiol, November 1, 2001; 281(5): F975 - F982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Brands, A. E. Hailman, and S. M. Fitzgerald Long-Term Glucose Infusion Increases Arterial Pressure in Dogs With Cyclooxygenase-2 Inhibition Hypertension, February 1, 2001; 37(2): 733 - 738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Rodriguez, M. T. Llinas, C. Moreno, and F. J. Salazar Role of Cyclooxygenase-2-Derived Metabolites and NO in Renal Response to Bradykinin Hypertension, January 1, 2001; 37(1): 129 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Llinas, F. Rodriguez, C. Moreno, and F. J. Salazar Role of cyclooxygenase-2-derived metabolites and nitric oxide in regulating renal function Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2000; 279(5): R1641 - R1646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hocherl, M. Kammerl, F. Kees, B. K. Kramer, H. F. Grobecker, and A. Kurtz Role of renal nerves in stimulation of renin, COX-2, and nNOS in rat renal cortex during salt deficiency Am J Physiol Renal Physiol, March 1, 2002; 282(3): F478 - F484. [Abstract] [Full Text] [PDF]
|
|