relevance Interaction between cyclooxygenase and the renin-angiotensin-aldosterone system: rationale and clinical

AbstractIncreased understanding of pathophysiological mechanisms of cardiovascular diseases has shown thatthe renin-angiotensin-aldosterone system (RAAS) isactivated in this setting and suggests a central role forthe angiotensin-converting enzyme (ACE). ACEtransforms angiotensin I (Ang I) to angiotensin II(Ang II), and also promotes the degradation ofbradykinin into inactive metabolites. Thesebradykinins stimulate nitric oxide synthesis andvasodilatator prostaglandin synthesis via a cyclooxygenase (COX) pathway.COX inhibitors may therefore be deleterious incardiovascular disease and/or counteract part of ACEinhibitor (ACE-I) efficacy. This has been clearlydemonstrated with non-steroidal anti-inflammatorydrugs (NSAIDs), including high-dose aspirin, inhypertension, coronary artery disease and chronicheart failure (CHF); most guidelines recommendavoiding their use in such patients.Theoretically, this effect is dose-mediated and theexistence 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 possibledeleterious effect and a counteraction of ACE-Is withlow-dose aspirin, using various criteria of assessment. However, there are no prospective long-termstudies 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 oflow-dose aspirin (100 mg/day) in such patients can berecommended.IntroductionThe renin-angiotensin-aldosterone system (RAAS)is an enzymatic cascade, which results mainly inthe synthesis of angiotensin II (Ang II).RAAS acti-vation plays a crucial role in the development andprogression of chronic heart failure (CHF), andmost recent therapeutic strategies, includingangiotensin-converting enzyme (ACE) inhibitors,Ang II receptor antagonists and β-blocking agents,target neurohormonal inhibition.