Coronary artery disease (CAD) and stroke will be the most common and critical long-term complications of hypertension. of cardioprotective ASA dosages. The advantage of mixed therapy with low-doses of ASA isin some casessignificantly greater than that of monotherapy. Up to now, the importance of ASA in optimizing the pharmacotherapy continues to be not established fully. A better knowledge of its impact on this CVD should contribute to more precise recognition of individuals 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. 1. Intro Activation of the renin-angiotensin-aldosterone system (RAAS) plays an important part in the pathogenesis of cardiovascular disorders, resulting in improved vascular resistance, excessive fluid retention, improved proliferation of vascular-smooth-muscle-cells, and cardiac hypertrophy. Inhibition of the bradykinin degradation, catalysed from RAD001 supplier the angiotensin transforming enzyme (ACE), results in improved prostacyclin launch and constitutes one of the additional mechanisms of the ACE inhibitors (ACE-I) antihypertensive effect. Bradykinin, physiologically degraded by ACE, is accumulated resulting in vasodilatation, which is definitely partially dependent on the prostanoid metabolic pathways, nitric oxide, and endothelium-derived hyperpolarizing element (EDHF). The cyclooxygenase (COX) inhibitors impact the above-mentioned mechanisms and may limit some beneficial effects of ACE-I. This in turn might be important in individuals with hypertension, coronary artery disease (CAD), and congestive heart failure (CHF). These observations apply to most of nonsteroidal anti-inflammatory medicines (NSAIDs) and aspirin (acetylsalicylic acid, ASA) at high doses. Nevertheless, there is no strong evidence, based on the long-term prospective studies, confirming the presence of related effects of ASA when given in small, cardioprotective doses [1]. 2. Renin-Angiotensin-Aldosterone System and the Cyclooxygenase Metabolic Pathway Recent studies have clearly demonstrated RAD001 supplier the part of aldosterone in the pathogenesis of systemic swelling, endothelial dysfunction, and fibrosis [2, 3]. It has also been shown that the effects of mineralocorticoids are present not only in the kidneys and that they are synthesized also outside the adrenal cortex [4]. Aldosterone acts on the cardiovascular system and also on the mechanisms independent of blood pressure regulation. It has been proven that the pharmacological blockade of its receptor exerts protective effects on the cardiovascular system, even while maintaining a constant value of blood pressure [5, 6]. A large amount of data indicates the participation of COX-dependent pathways in the pathogenesis of endothelial dysfunction induced by aldosterone. Its development is also possible in the normotension, and it is suppressed by both aldosterone receptor blockade and the COX inhibition [7]. Further analysis of the connections between these elements has shown that the thromboxane (TX) receptor blockade reduces the severity of endothelial dysfunction induced by aldosterone, but similar results were not observed for the inhibition of its synthesis. The increased production of TXA2 by vessels with aldosterone-induced endothelial dysfunction has also been shown, whichin combination with the previously cited observationswould indicate the TXA2 as an integral mediator in advancement of aldosterone-mediated endothelial dysfunction. Nevertheless, considering the known truth how the thromboxane synthesis inhibitors usually do not inhibit the vascular a reaction to acetylcholine, it really RAD001 supplier is postulated how the TX doesn’t have a substantial pathogenic part, which has other prostanoids performing through the TX receptor [8C11]. Prostacyclin (PGI), through the identified vasodilatory actions apart, can pave the pressor TX receptors effectviathe, which occurs, for example, in the RAD001 supplier aorta, where PGI appears to have, following towards the PGH2, the biggest share in the experience of EDCF [12, 13]. Rabbit Polyclonal to RAB41 Furthermore, it’s been demonstrated that using circumstances the inhibition of prostacyclin synthesis can enhance the diastolic reactivity from the vessel. Relating to Blanco-Rivero [7], contact with aldosterone induces endothelial dysfunctionviaactivation of COX-2 both in case there is initially normal blood circulation pressure as well as with experimental types of hypertension. In the.