Interaction between cyclooxygenase and the renin-angiotensin-aldosterone system: rationale and clinical relevance.
Increased understanding of pathophysiological mechanisms of cardiovascular diseases has shown that the renin-angiotensin-aldosterone system (RAAS) is activated in this setting and suggests a central role for the angiotensin-converting enzyme (ACE). ACE transforms angiotensin I (Ang I) to angiotensin II (Ang II), and also promotes the degradation of bradykinin into inactive metabolites. These bradykinins stimulate nitric oxide synthesis and vasodilatator prostaglandin synthesis via a cyclooxygenase (COX) pathway. COX inhibitors may therefore be deleterious in cardiovascular disease and/or counteract part of ACE inhibitor (ACE-I) efficacy. This has been clearly demonstrated with non-steroidal anti-inflammatory drugs (NSAIDs), including high-dose aspirin, in hypertension, coronary artery disease and chronic heart failure (CHF); most guidelines recommend avoiding their use in such patients. Theoretically, this effect is dose-mediated and the existence of an identical deleterious effect with low-dose aspirin has been an area of intense debate. In this article, we review studies, most of them conducted in CHF, that pointed out such a possible deleterious effect and a counteraction of ACE-Is with low-dose aspirin, using various criteria of assessment. However, there are no prospective long-term studies that have validated such an effect, and the role of other anti-aggregating agents has not been evaluated. Until such studies are published, the use of low-dose aspirin (100 mg/day) in such patients can be recommended.
Meune
Christophe
C
Department of Cardiology, Cochin Hospital, Rene Descartes University, Paris, France.
Mourad
Jean-Jacques
JJ
Bergmann
Jean-François
JF
Spaulding
Christian
C
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011451:Prostaglandin-Endoperoxide Synthases