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English Abstract
Journal Article
Review
[Oral inhibitors of renin and their potential use as therapeutic agents in treating hypertension].
Harefuah 2008 June
Hypertension is the most common risk factor for cardiovascular disease, constituting the most common cause of death in industrialized countries. Therefore, the task of blood pressure reduction has significant importance in reducing vascular damage, myocardial infarctions, kidney damage and incidence of cerebrovascular accidents. The renin-angiotensin-aldosterone system (RAAS) plays a central role in control and function of the cardiovascular and renal systems, and is deeply involved in the pathophysiology of diseases of vasculature, heart, kidneys and others. Therefore, blockade of RAAS by angiotensin converting enzyme (ACE) inhibitors and blockers of angiotensin II type AT1 receptors (ARBs) is widely utilized by clinicians. Indeed, it has long been known that ACE inhibitors and ARBs protect different targets of angiotensin II, due to impedance of the negative effects of the hormone and the inhibition of aldosterone production, which contributes both directly and indirectly to the damages, independent of angiotensin II. Despite this, the morbidity and mortality resulting from the progression of cardiovascular diseases in patients treated with ACE inhibitors or ARBs remain high. As such, over the years, much effort has been dedicated to the development of direct inhibitors of renin. The earliest renin inhibitors, developed 30 years ago were not effective due to their protein nature, which prevents their oral administration and limited their clinical use. In the last decade, several non-protein renin inhibitors which could be given orally were developed, of which Aliskiren is the most well known representative. Due to the fact that neutralization of the RAAS by ACE inhibitors and ARBs has been reviewed at length many times, this review will focus on the renewed subject of renin inhibition. The earliest research, both in humans as well as in animal models, show that Aliskiren has therapeutic potential in treatment of patients with hypertension, cardiovascular disease and renal disease. However, the efficacy of Aliskiren in treating systolic and diastolic hypertension in patients was not better than that obtained using ACE inhibitors or ARBs. Even so, there is no need to lower levels of optimism for potential therapy using direct inhibitors of renin. Current research is still in its early stages and there is a need to remember that it took many years to prove the clinical usefulness of ACE inhibitors, which are now central to treatment of cardiovascular and renal diseases, including hypertension.
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