LETTERS TO THE EDITOR
Reply
Richard J. Bing, MDa
a Department of Experimental CardiologyHuntington Medical Research Institutes99 North El Molino Avenue, Pasadena, California, 91101USA
White, in his response to our study "Cyclooxygenase (COX-2) Inhibitors and Cardiovascular Thromboembolic Events," stated "there are no clinical outcome data that support the hypothesis and statement of Bing and Lomnicka that the COX-2 inhibitor celecoxib causes cardiovascular events." We have indeed no clinical material of our own that demonstrates the effect of this selective nonsteroidal anti-inflammatory compound (NSAID) on cardiac events. But it was not our purpose to cite clinical material of our own in support of the effects of celecoxib. Rather, we attempted to demonstrate an experimental basis for the clinical trials by Mukherjee et al. (1). We primarily wanted to stress the importance of changes in prostanoids in heart muscle, specifically of thromboxane and prostacyclin. Prostacyclin is a vasodilator that prevents cardiac arrhythmias and platelet aggregation; thromboxane, in contrast, acts as a vasoconstrictor initiating ventricular arrhythmias (2). Therefore, in the heart a decline in prostacyclin results in coronary vasoconstriction, as does an increase in thromboxane. In the kidney, a disproportionate decline in prostacyclin has even more dire consequences (3), because both nonselective and selective NSAIDs cause acute renal failure (4–6). Changes in prostanoids in heart and kidney are related to the activity of cyclooxygenases (COX), which catalyze the conversion of arachidonic acid.
It was not our intention to present clinical evidence about the effect of celecoxib. Rather, we wanted to stress reasons for the possible relationship of NSAIDs to cardiac events. The decline in prostacyclin following administration of NSAIDs and the resulting deterioration in function confirm the predominant role of prostanoids in organ function.
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References
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1. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA. 2001;286:954–959[Abstract/Free Full Text]
2. Smith WL, Garavito RM, DeWitt DL. Prostaglandin endoperoxide-h synthases (cyclooxygenases)-1 and -2. J Biol Chem. 1996;271:33157–33160[Free Full Text]
3. Miyataka M, Rich KA, Ingram M, Yamamoto T, Bing RJ. Nitric oxide, anti-inflammatory drugs on renal prostaglandins and cyclooxygenase-2. Hypertension. 2002;39:785–789[Abstract/Free Full Text]
4. Dunn MJ. Are COX-2 selective inhibitors nephrotoxic? Am J Kidney Dis. 2000;35:976–977[Medline]
5. Perazella MA, Eras J. Are selective COX-2 inhibitors nephrotoxic? Am J Kidney Dis. 2000;35:937–940[Medline]
6. Whelton A. Cyclooxygenase-2 inhibition and renal function. Ann Intern Med. 2001;134:1077–1078[Free Full Text]
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