Interactions between the Cyclooxygenase Metabolic Pathway and the Renin-Angiotensin-Aldosterone Systems: Their Effect on Cardiovascular Risk, from Theory to the Clinical Practice

Abstract

Coronary artery disease (CAD) and stroke are the most common and serious long-term complications of hypertension. Acetylsalicylic acid (ASA) significantly reduces their incidence and cardiovascular mortality. The RAAS activation plays an important role in pathogenesis of CVD, resulting in increased vascular resistance, proliferation of vascular-smooth-muscle-cells, and cardiac hypertrophy. Drugs acting on the renin-angiotensin-aldosterone system (RAAS) are demonstrated to reduce cardiovascular events in population with cardiovascular disease (CVD). The cyclooxygenase inhibitors limit the beneficial effect of RAAS-inhibitors, which in turn may be important in subjects with hypertension, CAD, and congestive heart failure. These observations apply to most of nonsteroidal anti-inflammatory drugs and ASA at high doses. Nevertheless, there is no strong evidence confirming presence of similar effects of cardioprotective ASA doses. The benefit of combined therapy with low-doses of ASA is—in some cases—significantly higher than that of monotherapy. So far, the significance of ASA in optimizing the pharmacotherapy remains not fully established. A better understanding of its influence on the particular CVD should contribute to more precise identification of patients in whom benefits of ASA outweigh the complication risk. This brief review summarizes the data regarding usefulness and safety of the ASA combination with drugs acting directly on the RAAS.

Repurposing existing drugs for COVID-19: an endocrinology perspective

“…In addition of its regular use to prevent cardiovascular disease in those at high risk, aspirin may prevent gastrointestinal tract cancers [200][201][202] and participate in a wide range of different disorders [203], although its effects are highly dependent on the timing and dose administered [204]. While low doses aspirin may play indirect beneficial effects in the RAAS, including suppression of angiotensin II actions, high doses (> 200 mg/day) may hamper cardioprotective and lungprotective effects of the majority of drugs that address RAAS [205][206][207]. In the lungs, AAS may confer protective effects on the severity of lung injury induced by any endotoxin, and also lower the risk of ARDS, in particular in those previously using aspirin [207][208][209].…”

An Outline of Renal Artery Stenosis Pathophysiology—A Narrative Review

“…The disturbed activity of the next important pro-inflammatory and vasoactive mediators acting via autocrine and paracrine manner, i.e., the prostaglandin system, should also be mentioned in the context of complex RAS pathophysiology. The participation of the prostaglandins in RAS pathophysiology indirectly results from the fact that some action determined by bradykinin is mediated by the prostacyclin [ 75 ]. The prostaglandin system is, therefore, the next functional network, closely related to RAAS and kinins, and the changes in RAAS activity need to be considered in the broad context of the potential impact on other components.…”

“…The conditions with hyperreninemia due to the reduction in sodium chloride amount in ultrafiltrate (e.g., salt deficiency, administration od diuretics or ACEI/ARB) are associated with an increase in the expression and enzymatic activity of COX-2 in the kidneys. On the contrary, AII decreases COX-2 expression within the JG by stimulating the Na + /K + /2Cl − cotransporter and increasing intracellular sodium chloride concentration [ 75 , 79 ]. In in vitro studies, the use of PGE2 and PGI2 stimulate renin release in cultures of the JG apparatus cells.…”

Tratamento hipertensivo nefroprotetor

“…Tratamento anti-hipertensivo nefroprotetor nas Nefropatias Diabéticas Além disso, em diversos estudos, a exclusão de pacientes em ensaios clínicos decorreu, na maioria das vezes, de hipercalemia ou dano renal agudo, especialmente relacionados ao IECA 22 .…”