During the last 20 years, the renin-angiotensin system (RAS) has become an increasingly important focus of basic and clinical cardiovascular research. One main conceptual step forward was made with the discovery of a tissue RAS and the understanging of its critical pathophysiological role in atherogenesis and plaque destabilisation . Major effort to find new strategies for blocking the RAS has produced new classes of drugs which were expected to be clinically important in the management of hypertension and heart failure. As landmark clinical studies have demonstrated that inhibition of the RAS significantly reduces morbidity and mortality from coronary heart disease, myocardial infarction and heart failure, the concept has rapidly emerged that blocking the RAS was the strategy of choice for preventing cardiovascular diseases . More recently, basic research has however continuously extended our understanding of the complexity of the systemic and tissue RASs, that can no longer be viewed as one-way streets in which one single effector, angiotensin II acts solely through its major (AT1) receptor. Meanwhile, clinical trials have challenged the concept that blocking the RAS is the most effective preventive strategy for all patients and all target organs . Consistent with the recent understanding that the RAS encompasses a number of distinct effectors acting through different receptors to promote opposite effects, a growing body of basic and clinical evidence suggests that blunting the RAS is a double-edge sword, with beneficial effects counterbalanced by deleterious ones, resulting in a net effect that critically depends on the experimental conditions, or the clinical characteristics of the study population. Of particular clinical relevance, a number of clinical trials point to the somewhat provocative conclusion that beyond their blood pressure lowering effect antihypertensive drugs that decrease angiotensin II formation are less stroke protective than the ones that increase angiotensin levels . This review focuses on the recent experimental evidence demonstrating that angiotensin II and its derivatives acting through the non-AT1 receptors are involved in protective mechanisms against cerebral ischaemia and discusses in the light of the recent large cardiovascular prevention trials the clinical relevance of this new concept. The perspective of a renewal of therapeutical strategies to optimise the prevention of target organ damage and perhaps even some of the diseases of ageing, such as loss of cognitive function is emphasised.
Keywords: angiotensin converting enzyme, angiotensin peptides, blood pressure regulation, cardiovascular remodelling, ischemia
Antihypertensive Properties of Angiotensin-Converting Enzyme Inhibitors (ACEI) Independent of the Renin-Angiotensin System
Current Hypertension Reviews Use of Diuretics in Women for Management of Hypertension
Current Hypertension Reviews Lipid Management and Peripheral Arterial Disease
Current Drug Targets N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP): Potential target molecule in research of heart, kidney and brain
Current Pharmaceutical Design Eplerenone, a New Selective Aldosterone Blocker
Current Pharmaceutical Design Classical and New Renin-Angiotensin Signalling in Atherosclerosis
Current Signal Transduction Therapy Microparticles: From Biogenesis to Biomarkers and Diagnostic Tools in Cardiovascular Disease
Current Stem Cell Research & Therapy Cell Cycle Dependent Regulation of Intracellular Calcium Concentration in Vascular Smooth Muscle Cells: A Potential Target for Drug Therapy
Current Drug Targets - Cardiovascular & Hematological Disorders Cardiovascular Morbidity and Mortality in Peripheral Arterial Disease
Current Drug Targets - Cardiovascular & Hematological Disorders Is Impaired Flow-Mediated Dilatation of the Brachial Artery a Cardiovascular Risk Factor?
Current Vascular Pharmacology High Sensitivity C-Reactive Protein (hsCRP): A New Biochemical Marker of Atherosclerotic Vascular Disease
Current Cardiology Reviews Pre-eclampsia Versus Cardiovascular Disease Versus CRP
Current Hypertension Reviews Current Updates in the Medical Management of Obesity
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Under Re-organization) Development and Evaluation of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and Polycaprolactone Microparticles of Nimodipine
Current Pharmaceutical Design Nothing But Stress – The Interplay of Angiotensin II, Inflammation, Hypertension and Atherosclerosis: Implications for Atherosclerotic Plaque Stability
Vascular Disease Prevention Obstructive Sleep Apnoea Syndrome and Diabetes. Fortuitous Association or Interaction?
Current Diabetes Reviews Endothelin-1 and Human Platelets
Current Vascular Pharmacology Selective Serotonin-norepinephrine Re-uptake Inhibition Limits Renovas-cular-hypertension Induced Cognitive Impairment, Endothelial Dysfunction, and Oxidative Stress Injury
Current Neurovascular Research New Insights in Congenital Diaphragmatic Hernia
Current Respiratory Medicine Reviews Dehydrogenases/Reductases for the Synthesis of Chiral Pharmaceutical Intermediates
Current Organic Chemistry