Published online before print November 3, 2003, doi: 10.1161/01.CIR.0000101683.30157.0B
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2003;108:2308.)
© 2003 American Heart Association, Inc.
Brief Rapid Communications |
Differential Effects of Selective Cyclooxygenase-2 Inhibitors on Endothelial Function in Salt-Induced Hypertension
From Cardiology, Cardiovascular Center, University Hospital Zürich, the Institute of Physiology, University of Zürich-Irchel (M.H., G.C., A.F., F.C.T., J.P.H., T.F.L., F.R.), and the Center for Experimental Rheumatology, University Hospital Zürich, Switzerland (M.N., R.G., S.G.); and the Institute of Clinical Chemistry, University of Leipzig, Germany (M.F., J.T.).
Correspondence to Frank Ruschitzka, MD, FESC, Cardiology, University Hospital Zürich, 8091 Zürich, Switzerland. E-mail frank.ruschitzka{at}usz.ch
Received August 4, 2003; revision received September 19, 2003; accepted September 22, 2003.
Background— In view of the ongoing controversy about potential differences in cardiovascular safety of selective cyclooxygenase (COX)-2 inhibitors (coxibs), we compared the effects of 2 different coxibs and a traditional NSAID on endothelial dysfunction, a well-established surrogate of cardiovascular disease, in salt-induced hypertension.
Methods and Results— Salt-sensitive (DS) and salt-resistant (DR) Dahl rats were fed a high-sodium diet (4% NaCl) for 56 days. From days 35 to 56, diclofenac (6 mg · kg-1 · d-1; DS-diclofenac), rofecoxib (2 mg · kg-1 · d-1; DS-rofecoxib), celecoxib (25 mg · kg-1 · d-1; DS-celecoxib) or placebo (DS-placebo) was added to the chow. Blood pressure increased with sodium diet in the DS groups, which was more pronounced after diclofenac and rofecoxib treatment (P<0.005 versus DS-placebo) but was slightly decreased by celecoxib (P<0.001 versus DS-placebo). Sodium diet markedly reduced NO-mediated endothelium-dependent relaxations to acetylcholine (10-10-10-5 mol/L) in aortic rings of untreated hypertensive rats (P<0.005 versus DR-placebo). Relaxation to acetylcholine improved after celecoxib (P<0.005 versus DS-placebo and DS-rofecoxib) but remained unchanged after rofecoxib and diclofenac treatment. Vasoconstriction after nitric oxide synthase inhibition, indicating basal NO release, with N
-nitro-L-arginine methyl ester (10-4 mol/L) was blunted in DS rats (P<0.05 versus DR-placebo), normalized by celecoxib, but not affected by rofecoxib or diclofenac. Indicators of oxidative stress, 8-isoprostane levels, were elevated in untreated DS rats on 4% NaCl (6.55±0.58 versus 3.65±1.05 ng/mL, P<0.05) and normalized by celecoxib only (4.29±0.58 ng/mL).
Conclusions— These data show that celecoxib but not rofecoxib or diclofenac improves endothelial dysfunction and reduces oxidative stress, thus pointing to differential effects of coxibs in salt-induced hypertension.
Key Words: endothelium • drugs, antiinflammatory • hypertension • nitric oxide • stress
This article has been cited by other articles:
 |
|
 |
|
  L. I. Brueggemann, A. R. Mackie, B. K. Mani, L. L. Cribbs, and K. L. Byron Differential Effects of Selective Cyclooxygenase-2 Inhibitors on Vascular Smooth Muscle Ion Channels May Account for Differences in Cardiovascular Risk Profiles Mol. Pharmacol., November 1, 2009; 76(5): 1053 - 1061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Li, M. Hortmann, A. Daiber, M. Oelze, M. A. Ostad, P. M. Schwarz, H. Xu, N. Xia, A. L. Kleschyov, C. Mang, et al. Cyclooxygenase 2-Selective and Nonselective Nonsteroidal Anti-Inflammatory Drugs Induce Oxidative Stress by Up-Regulating Vascular NADPH Oxidases J. Pharmacol. Exp. Ther., September 1, 2008; 326(3): 745 - 753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Aneja and M. E. Farkouh Review: Adverse cardiovascular effects of NSAIDs: driven by blood pressure, or edema? Therapeutic Advances in Cardiovascular Disease, February 1, 2008; 2(1): 53 - 66. [Abstract] [PDF]
|
|
|
|
 |
|
 G. P. Joshi, R. Gertler, and R. Fricker Cardiovascular Thromboembolic Adverse Effects Associated with Cyclooxygenase-2 Selective Inhibitors and Nonselective Antiinflammatory Drugs Anesth. Analg., December 1, 2007; 105(6): 1793 - 1804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Klein, M. Eltze, T. Grebe, A. Hatzelmann, and M. Komhoff Celecoxib dilates guinea-pig coronaries and rat aortic rings and amplifies NO/cGMP signaling by PDE5 inhibition Cardiovasc Res, July 15, 2007; 75(2): 390 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. B. White Cardiovascular Effects of the Cyclooxygenase Inhibitors Hypertension, March 1, 2007; 49(3): 408 - 418. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hermann and F. Ruschitzka Novel anti-inflammatory drugs in hypertension Nephrol. Dial. Transplant., April 1, 2006; 21(4): 859 - 864. [Full Text] [PDF]
|
|
|
|
 |
|
 N. E. Taylor and A. W. Cowley Jr. Effect of renal medullary H2O2 on salt-induced hypertension and renal injury Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1573 - R1579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hermann, H. Krum, and F. Ruschitzka To the Heart of the Matter: Coxibs, Smoking, and Cardiovascular Risk Circulation, August 16, 2005; 112(7): 941 - 945. [Full Text] [PDF]
|
|
|
|
|
|
R. Wu, M.-A. Laplante, and J. de Champlain Cyclooxygenase-2 Inhibitors Attenuate Angiotensin II-Induced Oxidative Stress, Hypertension, and Cardiac Hypertrophy in Rats Hypertension, June 1, 2005; 45(6): 1139 - 1144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Steffel, M. Hermann, H. Greutert, S. Gay, T. F. Luscher, F. Ruschitzka, and F. C. Tanner Celecoxib Decreases Endothelial Tissue Factor Expression Through Inhibition of c-Jun Terminal NH2 Kinase Phosphorylation Circulation, April 5, 2005; 111(13): 1685 - 1689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Kimmel, J. A. Berlin, M. Reilly, J. Jaskowiak, L. Kishel, J. Chittams, and B. L. Strom Patients Exposed to Rofecoxib and Celecoxib Have Different Odds of Nonfatal Myocardial Infarction Ann Intern Med, February 1, 2005; 142(3): 157 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Finckh and M. D. Aronson Cardiovascular Risks of Cyclooxygenase-2 Inhibitors: Where We Stand Now Ann Intern Med, February 1, 2005; 142(3): 212 - 214. [Full Text] [PDF]
|
|
|
|
|
|
I. J. Chang and R. C. Harris Are All COX-2 Inhibitors Created Equal? Hypertension, February 1, 2005; 45(2): 178 - 180. [Full Text] [PDF]
|
|
|
|
|
|
M. Hermann, S. Shaw, E. Kiss, G. Camici, N. Buhler, R. Chenevard, T. F. Luscher, H. J. Grone, and F. Ruschitzka Selective COX-2 Inhibitors and Renal Injury in Salt-Sensitive Hypertension Hypertension, February 1, 2005; 45(2): 193 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. N. Bratz and N. L. Kanagy Nitric oxide synthase-inhibition hypertension is associated with altered endothelial cyclooxygenase function Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2394 - H2401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Solomon, S. Schneeweiss, R. Levin, and J. Avorn Relationship Between COX-2 Specific Inhibitors and Hypertension Hypertension, August 1, 2004; 44(2): 140 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Gates, H. Tanaka, W. R. Hiatt, and D. R. Seals Dietary Sodium Restriction Rapidly Improves Large Elastic Artery Compliance in Older Adults With Systolic Hypertension Hypertension, July 1, 2004; 44(1): 35 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Solomon, S. Schneeweiss, R. J. Glynn, Y. Kiyota, R. Levin, H. Mogun, and J. Avorn Relationship Between Selective Cyclooxygenase-2 Inhibitors and Acute Myocardial Infarction in Older Adults Circulation, May 4, 2004; 109(17): 2068 - 2073. [Abstract] [Full Text] [PDF]
|
|