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

Abstract

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)

High-density Lipoprotein Cholesterol Levels and Prognosis in Advanced Heart Failure

“…13 Further evidence of their importance in maintaining compensation in HF was found in clinical data on non-steroidal anti-inflammatory drug use, which demonstrated deterioration as a consequence of prostaglandin inhibition. 14 When severity of HF advances, it leads to a decline in serum sodium levels, a reflection of heightened reninangiotensin-aldosterone pathway activation. 13 It has been demonstrated that the prostaglandin pathway begins to counteract these deleterious pathways and hyponatremic patients demonstrate increased prostanoid metabolites in the circulation.…”

Comparative effect of aspirin and clopidogrel on arterial function in CHF

“…Bradykinin stimulates nitric oxide (NO) and also vasodilator prostaglandins (PG) synthesis via a cyclooxygenase (COX) pathway [7]. Theoretically, COX inhibitors, including aspirin, may partially counteract the efficacy of ACEI but also directly inhibit endogenous vasodilator PG synthesis and/or enhance the vasoconstrictor potential of endothelin [8][9][10], and so have a deleterious effect in CHF. This adverse effect may be even more relevant in severe CHF where bradykinins are stimulated in order to counteract enhancement of vasoconstrictor tone [11,12].…”

Aspirin Inhibits the Acute Arterial and Venous Vasodilator Response to Captopril in Patients with Chronic Heart Failure

“…Furthermore, some retrospective analyses have demonstrated a negative interaction between these two types of drug, whereby aspirin attenuates the morbidity-mortality benefit of ACE inhibitors [7][8][9][10]. Other reports have not confirmed this interaction though their analysis and interpretation has been disputed and this issue remains controversial [7,9,[11][12][13]. Some studies have also shown a deleterious effect of aspirin on the hemodynamic response ACE inhibitors [3,4,14].…”

“…These studies, however, have mainly investigated high doses (>150 mg daily) of aspirin, whereas, in clinical practice, the majority of patients now receive low dose aspirin [10]. An unresolved and clinically important question is, therefore, whether a low dose of aspirin (the dose used in atherosclerotic disease for secondary prevention) counteracts the hemodynamic effects of ACE inhibitors (which may contribute to the benefits of these drugs) in patients with CHF [9]. This study was designed to investigate that question.…”

“…Not all agree, however, that the benefits of aspirin extend to patients with CHF [6]. Furthermore, some retrospective analyses have demonstrated a negative interaction between these two types of drug, whereby aspirin attenuates the morbidity-mortality benefit of ACE inhibitors [7][8][9][10]. Other reports have not confirmed this interaction though their analysis and interpretation has been disputed and this issue remains controversial [7,9,[11][12][13].…”