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Blood pressure effects of COX-2 inhibitors
Henry Krum1, Tai-Juan Aw, Danny Liew
1NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. henry.krum@med.monash.edu.au
Abstract:
There has been significant recent interest in the cardiovascular effects of cyclooxygenase 2 (COX-2) selective inhibitors. Whereas much attention has been focused on the putative prothrombotic effect of these agents, their cardiorenal and blood pressure elevating actions may be of equal if not greater importance to cardiovascular risk. COX-2 is widely expressed throughout the kidney, and inhibition of this enzyme is contributory to reduced glomerular filtration, salt and water retention, and blood pressure elevation. The key issues in relation to COX-2 inhibitors and blood pressure are whether these blood pressure-elevating effects are similar to or differ from nonselective nonsteroid anti-inflammatory drugs, whether differences exist among COX-2 inhibitors in regard to blood pressure regulation, and if so, possible mechanisms underlying blood pressure differences between COX-2 inhibitors. With regard to the last issue, possible mechanisms include greater COX-2 selectivity of certain agents such as rofecoxib, the differing half-life of these agents, the carbonic anhydrase activity of celecoxib (which may offset renal-induced salt and water retention), and possible aldosterone modulation by rofecoxib. Finally, and perhaps most important, the issue arises as to whether blood pressure elevation may contribute in whole or in part to the increase in cardiovascular events observed with these agents in some but not all studies. Ultimately, adequately powered, prospective randomized clinical trials assessing relevant cardiovascular endpoints are required to address many of these outstanding questions. Such studies have recently been announced and will commence soon.
Insights
Cyclooxygenase 2 (COX-2) inhibitors can elevate blood pressure and affect cardiorenal function, potentially increasing cardiovascular risk. Further clinical trials are needed to fully understand these effects and their impact on patient outcomes.
Area of Science:
- Cardiovascular Pharmacology
- Renal Physiology
- Drug Safety
Background:
- Cyclooxygenase 2 (COX-2) selective inhibitors are under scrutiny for cardiovascular effects.
- While prothrombotic risks are known, cardiorenal and blood pressure effects are also critical.
- COX-2 inhibition in the kidney impacts glomerular filtration, salt/water balance, and blood pressure.
Purpose of the Study:
- To investigate the blood pressure-elevating actions of COX-2 inhibitors.
- To compare these effects with nonselective NSAIDs and among different COX-2 inhibitors.
- To explore potential mechanisms behind observed blood pressure differences.
Main Methods:
- Review of existing literature on COX-2 inhibitors and cardiovascular/renal effects.
- Analysis of potential mechanisms including COX-2 selectivity, drug half-life, carbonic anhydrase activity, and aldosterone modulation.
- Discussion of the contribution of blood pressure elevation to cardiovascular events.
Main Results:
- COX-2 inhibition contributes to reduced glomerular filtration, salt/water retention, and hypertension.
- Potential mechanisms for blood pressure differences among COX-2 inhibitors include selectivity, half-life, carbonic anhydrase activity (celecoxib), and aldosterone modulation (rofecoxib).
- The role of blood pressure elevation in cardiovascular events associated with COX-2 inhibitors requires further investigation.
Conclusions:
- The cardiorenal and blood pressure effects of COX-2 inhibitors are significant considerations for cardiovascular risk.
- Differences in blood pressure regulation may exist among COX-2 inhibitors due to varying mechanisms.
- Prospective, randomized clinical trials are essential to definitively address these cardiovascular concerns.
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