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      Effect of angiotensin II blockade on central blood pressure and arterial stiffness in subjects with hypertension

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          Abstract

          In hypertension, the blood pressure curve may be divided into two sets of components. The first set is mean arterial pressure, steady flow, and vascular resistance, thus acting on small arteries; the second set refers to large arteries, hence to pulse pressure, arterial stiffness, and wave reflections. The angiotensin-converting enzyme (ACE) inhibitor perindopril not only reduces mean arterial pressure but also acts specifically on pulse pressure. The effect on pulse pressure predominates on central rather than peripheral (brachial) large arteries, reducing aortic stiffness and most wave reflections. Such hemodynamic changes are not observed with standard β-blockade, which reduces aortic stiffness and brachial systolic and pulse pressure but not central pulse pressure and wave reflections. In hypertensive subjects, perindopril and other ACE inhibitors seem to predict more consistently the reduction of cardiovascular events, mainly of cardiac origin, than standard β-blockers alone. This effect is associated with the important biochemical finding that mechanotransductions of angiotensin and β-blockade are markedly different, acting in the former specifically on the α5β1 integrin complex and on the fibronectin ligand of arterial vessels.

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          Most cited references35

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          Integrins as mechanochemical transducers.

          D. Ingber (1991)
          A recent resurgence of interest in mechanical forces and cell shape as biological regulators has revealed extracellular matrix as the site at which forces are transmitted both to and from cells. at the same time, great advances have been made in terms of defining cell-surface integrin receptors as transmembrane molecules that mediate cell attachment and physically interlink extracellular matrix with the intracellular cytoskeleton. Convergence of these two lines of research has begun to elucidate the molecular mechanism by which cells sense physical forces and transduce mechanical signals into a biochemical response.
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            Structure and mechanical properties of resistance arteries in hypertension: role of adhesion molecules and extracellular matrix determinants.

            Abnormalities of resistance arteries may play a role in the pathogenesis and pathophysiology of hypertension in experimental animals and humans. Vessels that, when relaxed, measure <400 microm in lumen diameter act as the major site of vascular resistance and include a network of small arteries (lumen approximately 100 to 400 microm) and arterioles (<100 microm). Because increased peripheral resistance is generated by a narrowed lumen diameter, significant effort has been focused on determining the mechanisms that reduce lumen size. Three important vascular components are clearly involved, including alterations of vascular structure, mechanics (stiffness), and function. Structural abnormalities comprise a reduced lumen diameter and thickening of the vascular media, resulting in an increased media-lumen ratio. Changes in the mechanical properties of an artery, particularly increased stiffness, may also result in a reduced lumen diameter. These vascular abnormalities may be caused or influenced by the expression and/or topographic localization of extracellular matrix components, such as collagen and elastin, and by changes in cell-extracellular fibrillar attachment sites, such as adhesion molecules like integrins. This article discusses the abnormalities of resistance arteries in hypertension and reviews the evidence suggesting an important role for adhesive and extracellular matrix determinants.
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              Effect of different antihypertensive drug classes on central aortic pressure.

              Central aortic systolic blood pressure (BP) is an important determinant of cardiac workload and cardiac hypertrophy. The relationship of central aortic systolic BP and brachial BP varies depending on the stiffness of blood vessels. It is not certain whether the different drug classes affect the brachial and aortic systolic BP in a similar manner. In a double-blind crossover study, we measured the effects of the four major drug classes compared with placebo on central aortic pressure. Central aortic pressure and various indices were determined using the Sphygmo Cor apparatus. The study was undertaken in patients aged 65 to 85 years with systolic BP >150 mm Hg at study entry. Results are reported for 32 patients who had satisfactory applanation tonometry in all five periods. Calcium channel blockers and diuretics caused a greater fall in brachial artery systolic BP than angiotensin-converting enzyme (ACE) inhibitors or beta-blocking drugs. On placebo, central aorta augmentation pressure and index were 23 mm Hg and 33.3%; on ACE inhibitors the values were 18 mm Hg and 30%; on beta-blockers, 26 mm Hg and 38.5%; on calcium channel blockers, 16 mm Hg and 28%; and on diuretics, 17 mm Hg and 28.8%. The augmentation pressure on beta-blocking drugs was greater than on the other three drug classes (P <.05), and augmentation pressures on ACE inhibitors, calcium channel blockers, and diuretics were less than on placebo (P <.05). The lowest central aortic pressures were achieved with calcium blocking drugs and diuretics. Therapy based on brachial artery recordings may thus overestimate the effect of beta-blocking drugs on central aortic systolic BP and underestimate the effectiveness of ACE inhibitors and calcium blocking drugs. The clinical importance of this discrepancy needs to be evaluated.
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                Author and article information

                Journal
                Int J Nephrol Renovasc Dis
                International Journal of Nephrology and Renovascular Disease
                Dove Medical Press
                1178-7058
                2010
                03 December 2010
                : 3
                : 167-173
                Affiliations
                Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, Hôtel-Dieu Centre de Diagnostic et de Thérapeutique, Paris, France
                Author notes
                Correspondence: Michel Safar, Diagnosis Center, Hôpital Hôtel-Dieu, 1 place du Parvis Notre-Dame, 75181 Paris Cedex 04, France, Tel +33 1 42 34 80 25, Fax +33 1 42 34 86 32, Email michel.safar@ 123456htd.aphp.fr
                Article
                ijnrd-3-167
                10.2147/IJNRD.S6664
                3108785
                21694942
                c9c770d7-6f2f-4e7f-bbfa-6a85fd864399
                © 2010 Safar, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                : 2 December 2010
                Categories
                Review

                Nephrology
                antihypertensive therapy,renal function,arterial stiffness
                Nephrology
                antihypertensive therapy, renal function, arterial stiffness

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