Effect of chronic ANG I-converting enzyme inhibition on aging processes. II. Large arteries

Michel, Jean‐Baptiste; Heudes, Didier; Michel, Odile; Poitevin, Pierre; Philippe, Monique; Scalbert, Elizabeth; Corman, B.; Levy, B. I.

doi:10.1152/ajpregu.1994.267.1.r124

Cited by 123 publications

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“…This parameter is dependent on cell size and cell number and in the aorta largely reflects the medial smooth muscle cells as endothelial cells and adventitial fibroblasts are proportionately minor constituents. This parameter has been shown to increase with aging in a manner similar to medial cell area measured by histomorphometry 20 and to decrease in the normotensive rat after inhibition of the renin-angiotensin system. 20,21 This phenotype, and the demonstration of its genetic control by gene(s) at the locus Acp1, is thus important in the context of vascular remodeling.…”

Section: Discussionmentioning

confidence: 61%

“…This parameter has been shown to increase with aging in a manner similar to medial cell area measured by histomorphometry 20 and to decrease in the normotensive rat after inhibition of the renin-angiotensin system. 20,21 This phenotype, and the demonstration of its genetic control by gene(s) at the locus Acp1, is thus important in the context of vascular remodeling. The BN strain has been widely used as a control normotensive strain in genetic studies related to hypertension.…”

Section: Discussionmentioning

confidence: 61%

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Chromosomal Mapping of Quantitative Trait Loci Controlling Elastin Content in Rat Aorta

et al. 2005

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Abstract-Extracellular matrix molecules such as elastin and collagens provide mechanical support to the vessel wall. In addition to its structural role, elastin is a regulator that maintains homeostasis through biologic signaling. Genetically determined minor modifications in elastin and collagen in the aorta could influence the onset and evolution of arterial pathology, such as hypertension and its complications. We previously demonstrated that the inbred Brown Norway (BN) rat shows an aortic elastin deficit in both abdominal and thoracic segments, partly because of a decrease in tropoelastin synthesis when compared with the LOU rat, that elastin gene polymorphisms in these strains do not significantly account for. After a genome-wide search for quantitative trait loci (QTL) influencing the aortic elastin, collagen, and cell protein contents in an F2 population derived from BN and LOU rats, we identified on chromosomes 2 and 14, 3 QTL specifically controlling elastin levels, and a further highly significant QTL on chromosome 17 linked to the level of cell proteins. We also mapped 3 highly significant QTL linked to body weight (on chromosomes 1 and 3) and heart weight (on chromosome 1) in the cross. This study demonstrates the polygenic control of the content of key components of the arterial wall. Such information represents a first step in understanding possible mechanisms involved in dysregulation of these parameters in arterial pathology. Key Words: aorta Ⅲ elastin Ⅲ genetics Ⅲ rats E lastin and collagens are the main extracellular matrix proteins of blood vessels. The functional properties of vessels, particularly of the major arteries and veins, are largely dependent on the absolute and relative quantities of these 2 constituents. 1 Elastic fibers composed of an elastin core surrounded by microfibrils are designed to maintain elastic function in tissues such as blood vessels, lungs, and skin. The biology of elastic fibers is complex because of their multiple components, tightly regulated developmental pattern of expression, multistep hierarchical assembly, unique elastomeric properties, and influence on cell phenotype.The elastin-null mice (ELN Ϫ/Ϫ ) die of obstructive arterial disease, 2 whereas the ELN ϩ/Ϫ mice have reduced absolute quantities of elastin and are hypertensive, phenotypes similar to those observed in patients with supravalvular aortic stenosis and Williams syndrome. In these patients, the elastin gene is mutated or deleted. 3,4 Investigating the genetic basis and pathophysiological consequences of the modulation of elastin levels, rather than the impact of absolute elastin deficit, is central to our understanding of mechanisms involved in arterial pathologies. The composition of the arterial extracellular matrix and the adaptative synthesis of elastin and collagen in hypertension may also influence the degree of reversibility of arterial remodeling in response to antihypertensive treatment and the development of hypertensive arteriopathy. Genetic studies of the aortic content of extracellu...

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 61%

Chromosomal Mapping of Quantitative Trait Loci Controlling Elastin Content in Rat Aorta

et al. 2005

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“…21 An age-associated increase in aortic angiotensin converting enzyme (ACE) activity occurs in rats 22 and nonhuman primates; aortic angiotensin II is increased and co-localizes with both increased ACE and MMP-2. 23 Importantly, many of the age-associated intimal and matrix changes can be markedly delayed by chronic administration of ACE inhibitors, 3 suggesting that ageassociated changes in the local vascular angiotensin system may play a central role in age-associated vascular remodeling.…”

Section: Vascular Responses To Injurymentioning

confidence: 99%

Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises

2003

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“…18,19 Studies in animal models show that arterial levels of angiotension-converting enzyme (ACE), Ang II, and AT 1 R increase with age 20 as do the downstream signaling events, including an upregulation of tumor growth factor-␤ and fibronectin production and activation of matrix metalloprotease II, a multitask protease that can activate growth factors and cleave elastin. 21 Chronic ACE inhibition markedly attenuates age-associated structural remodeling and stiffening in rodents, 22 and in hypertensive patients there is some evidence that ACE inhibitors decrease the arterial thickness independently of changes in blood pressure. 23 The reduction of diastolic pressure in older persons with PSH in the Gates et al study 8 indicates that a reduction in dietary NaCl intake reduces PVR.…”

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confidence: 99%

The Dietary Sodium-Blood Pressure Plot “Stiffens”

Bagrov

Lakatta

2004

Hypertension

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N early 50% of our population by 65 years of age has a systolic pressure within a "risky" range, that is, has predominantly systolic hypertension (PSH), 1 attributable, in part, to a reduction in large artery compliance because of an increased stiffness of the arterial wall. For a given pattern of left ventricular ejection, arterial stiffening reduces diastolic pressure and increases pulse pressure. Although increased arterial stiffness elevates pulse pressure, it is not itself sufficient to raise systolic pressure to hypertensive levels, unless accompanied by an increase in stroke volume or peripheral vascular resistance (PVR). 2 Whereas the former is not increased in older persons with PSH, the latter is higher (by Ϸ15% on average) than in age-matched normotensive persons. 3 This mild-moderate elevation of PVR is usually unrecognized because it is not routinely assessed. The increased large artery stiffness that accompanies PSH precedes the elevation of arterial pressure to clinically defined hypertensive values, 4 giving rise to the notion that this form of hypertension, at least in part, is a disease of the arterial wall. Moreover, elevated pulse wave velocity, an index of arterial stiffness, and reduced total systemic compliance, assessed by stroke volume/pulse pressure, are themselves independent predictors of future cardiovascular events, even after accounting for the effect of the concomitant increase in blood pressure. 5,6 There is substantial evidence to indicate that the NaCl dependence of arterial pressure increases with advancing age and that this age effect is exaggerated in older hypertensive patients. 7 In this issue of Hypertension, Gates et al 8 add to this perspective by demonstrating that a reduction in dietary sodium to approximately 60 mmol/d, considered to be a low sodium intake by the Dietary Approaches to Stop Hypertension (DASH) study, 9 effectively lowers arterial pressure in older persons with PSH. Gates et al 8 also confirm prior observations that reducing dietary NaCl increases arterial compliance and reduces arterial stiffness. 10 Of particular note is that both the compliance and stiffness effects were evident 1 to 2 weeks following a reduction in NaCl. 8 Although PVR was not measured in their study, the Gates et al results demonstrate that reduction in dietary NaCl reduces diastolic as well as systolic pressure in PSH; pulse pressure is also reduced. 8 In addition to its effect on arterial pressure, NaCl affects arterial stiffness by altering vascular structure and smooth muscle cell and endothelial cell function. Both clinical and experimental evidence indicate that NaCl induces hypertrophy of the arterial wall in the absence of changes in arterial pressure 11 and induces hypertrophy of cultured vascular cells. 12 Excessive NaCl intake reduces the bioavailability of nitric oxide by interfering with the induction of nitric oxide synthase; by increasing asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, 13 reducing the production of nitric oxide; and by el...

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Effect of chronic ANG I-converting enzyme inhibition on aging processes. II. Large arteries

Cited by 123 publications

References 0 publications

Chromosomal Mapping of Quantitative Trait Loci Controlling Elastin Content in Rat Aorta

Chromosomal Mapping of Quantitative Trait Loci Controlling Elastin Content in Rat Aorta

Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises

The Dietary Sodium-Blood Pressure Plot “Stiffens”

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