Vascular Structural and Functional Alterations Before and After the Development of Hypertension in SHR

Rizzoni, Damiano; Castellano, Maurizio; Porteri, Enzo; Bettoni, Giorgio; Muiesan, M.L.; Agabiti‐Rosei, Enrico

doi:10.1093/ajh/7.2.193

Cited by 88 publications

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“…Small artery structural alterations may precede the development of hypertension and may occur earlier than endothelial dysfunction. 2,38 In the remod- eled vessel, the chronically altered local pressure-flow relationship may result in adaptive resetting of the endothelium, resulting in blunting of the reduction in NO generation, as well as of the production of other endothelium-derived relaxants, and, therefore, relative preservation of endothelium-dependent relaxation. This may also counteract the deterioration of the structure of proximal resistance arteries from young subjects with moderate hypertension.…”

Section: Discussionmentioning

confidence: 99%

Selective Mineralocorticoid Receptor Blocker Eplerenone Reduces Resistance Artery Stiffness in Hypertensive Patients

Nazzaro

Federici

Lucivero

et al. 2007

High Blood Pressure & Cardiovascular Prevention

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Abstract-Some antihypertensive agents may improve resistance artery remodeling in hypertensive patients whereas other agents may not, for similar blood pressure reduction. We questioned whether the selective mineralocorticoid receptor blocker eplerenone improves resistance artery remodeling in hypertensive patients versus the ␤-blocker atenolol. Sixteen hypertensive patients were randomly assigned to double-blind daily treatment with eplerenone or atenolol. Resistance arteries from gluteal subcutaneous tissue were assessed on a pressurized myograph. After 1 year of treatment, systolic and diastolic blood pressures were similarly well controlled in both groups. Endothelial function did not change with treatment in either group. Media/lumen ratio and cross-sectional area were unchanged in either the atenolol or the eplerenone group. In atenolol-treated patients, the arterial wall became stiffer, whereas in the eplerenone-treated patients, it became less stiff and similar to that of a normotensive control group. The media collagen/elastin ratio was reduced only after eplerenone treatment. Circulating concentrations of osteopontin, monocyte chemoattractant protein-1, basic fibroblast growth factor, interleukin-8, and interleukin-10 were significantly reduced only by eplerenone. However, plasma interleukin-1 receptor a concentration was significantly reduced by both drugs. In conclusion, in hypertensive patients, blood pressure control for 1 year with atenolol was associated with increased wall stiffness of resistance arteries, whereas eplerenone treatment was associated with reduced stiffness, decreased collagen/elastin ratio, and a reduction in circulating inflammatory mediators. These data raise the possibility that eplerenone treatment of hypertensive patients when normalizing blood pressure could potentially be associated with better vascular protection and outcomes than the ␤-blocker atenolol, which remains to be demonstrated. Key Words: aldosterone Ⅲ vascular remodeling Ⅲ extracellular matrix Ⅲ collagen Ⅲ elastin Ⅲ inflammatory biomarkers N ormalization of elevated blood pressure (BP) in hypertensive individuals is associated with reduced targetorgan damage and incident cardiovascular morbidity and mortality. 1 Small artery structural alterations may precede many clinical manifestations of end-organ damage in hypertensive patients 2 and predict the occurrence of future cardiovascular events. 3 Activation of the renin-angiotensinaldosterone system has been associated with increased cardiovascular morbidity and mortality in hypertensive patients. We and others have shown that antihypertensive drugs that interfere with the renin-angiotensin-aldosterone system exert potentially beneficial effects on vascular structure beyond BP control in hypertensive patients at variable risk for cardiovascular disease 4 -7 by improving the functional and anatomic alterations of resistance arteries typically found in experimental and human hypertension and which participate in increased peripheral resistance.Aldosterone is a mine...

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Section: Discussionmentioning

confidence: 99%

Selective Mineralocorticoid Receptor Blocker Eplerenone Reduces Resistance Artery Stiffness in Hypertensive Patients

Nazzaro

Federici

Lucivero

et al. 2007

High Blood Pressure & Cardiovascular Prevention

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“…The following parameters were measured: wall thickness, media thickness, internal diameter, media to lumen ratio. For further details, see Rizzoni et al [12][13][14] and Vecchione et al 15 The functional characteristics of the vessels were then evaluated. The vessels were exposed three times to PSS with equimolar exchange of NaCl for KC1 (KPSS) (2 min, with a 10-min interval) to evaluate their response to potassium, the maximal response usually being observed during the third stimulation.…”

Section: Methodsmentioning

confidence: 99%

“…Wall tension (active force divided by two times the segment length) and active media stress (wall tension divided by media thickness) were then calculated. [12][13][14] If the vessels produced rhythmic activity, the response was measured from the mean active force for the last 20 s of each period.…”

Section: Methodsmentioning

confidence: 99%

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Functional alterations of mesenteric small resistance arteries in Milan hypertensive and normotensive rats

et al. 2009

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The Milan hypertensive rat strain (MHS) is a genetic strain in which cardiovascular phenotypes seem to be dependent, at least in part, on adducin gene polymorphisms. The aim of our study was to evaluate the structure, contractile responses and endothelium-dependent vasodilation in mesenteric small resistance arteries in 12-week-old MHS, (n¼7), age-matched Milan normotensive rats (MNS, n¼7) and congenic strains in which the DNA segments carrying the a-adducin locus from the MHS have been introgressed into the MNS (MNA, n¼7). Systolic blood pressure (tail cuff) and left ventricular weight to body weight were measured. Mesenteric small arteries were dissected and mounted on a micromyograph; the media:lumen ratio was then calculated. Concentration-response curves to acetylcholine and to norepinephrine (NE) were created. Systolic blood pressure was significantly increased in the MHS and MNA strains compared with the MNS. No significant difference in mesenteric small resistance artery structure was observed among the groups; however, a slightly more elevated media:lumen ratio was observed in MNA compared with the MNS. In contrast, left ventricular weight to body weight was significantly increased and ACH-induced dilatation was significantly impaired in the MHS and in MNA compared with MNS. The concentration-response curve to NE in the MHS showed significantly reduced sensitivity to NE; however, maximum contraction was increased in the MHS vs. the other groups. The MHS presents cardiac (but not vascular) remodeling, endothelial dysfunction and a peculiar contractile response to NE, compared with the other groups. The systolic blood pressure increase and trend to vascular remodeling in MNA support the pathogenic role of a-adducin.

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“…An increase in the media-to-lumen ratio in mesenteric small resistance arteries has been observed in SHR at a prehypertensive stage (4 weeks of age). 12 Norrelund et al 13 found that renal afferent arterioles are narrowed at a very young age in SHR. Interestingly, there was no correlation between renal afferent arteriolar diameter and blood pressure in SHR at 7 weeks of age, but the lumen reduction at 7 weeks correlated with blood pressure subsequently measured at 23 weeks.…”

Section: Microcirculatory Abnormalities In Hypertension: Both Cause Amentioning

confidence: 99%

Microcirculation in Hypertension

Ambrosio

Carluccio²,

Bentivoglio³

2003

Molecular Basis for Microcirculatory Disorders

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T he number of effective agents available for the treatment of hypertension is now substantial. However, in spite of this, most would agree that there is still considerable scope for improvement in the way hypertension is managed. In many countries, the great majority of hypertensive subjects still show imperfect blood pressure control. 1 Furthermore, the reductions or improvements in end-organ damage seen during antihypertensive therapy do not always correlate well with the reduction in arterial blood pressure achieved. Thus, there seems to be a need for new therapeutic perspectives in the treatment of hypertension. One important new perspective might be provided by an enhanced appreciation of the importance of the microcirculation in the pathophysiology and treatment of hypertension. Description of the MicrocirculationThe microcirculation is widely taken to encompass vessels Ͻ150 m in diameter. It therefore includes arterioles, capillaries, and venules. However, there is no universally accepted definition of the microcirculation, and it is not clear whether vessels that would be defined as small arteries on the basis of anatomical criteria but have diameters Ͼ150 m should also be included. A definition based on arterial vessel physiology rather than diameter or structure is therefore proposed, depending on the response of the isolated vessel to increased internal pressure. By this definition, all those arterial vessels that respond to increasing pressure by a myogenic reduction in lumen diameter would be included in the microcirculation, as well as the capillaries and venules. Such a definition would include the smallest arteries and arterioles in the microcirculation and would be in line with the recent suggestion that the small arterial and arteriolar components should be considered a continuum rather than distinct sites of resistance control. 2 Several aspects of the physiology of arterial vessels, including flow-dependent responses, are not restricted to particular vessel categories (Figure 1). 3 A primary function of the microcirculation is to optimize nutrient and oxygen supply within the tissue in response to variations in demand. A second important function is to avoid large fluctuations in hydrostatic pressure at the level of the capillaries causing disturbances in capillary exchange. Finally, it is at the level of the microcirculation that a substantial proportion of the drop in hydrostatic pressure occurs. The microcirculation is therefore extremely important in determining the overall peripheral resistance. 4,5 It is also the site where the earliest manifestations of cardiovascular disease-in particular, inflammatory processes-occur. There is now a very high level of clinical and research interest in the microcirculation, as demonstrated by the fact that over the last 3 years, Ͼ800 articles per year have been published in MEDLINE-listed journals on this topic. 6

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Vascular Structural and Functional Alterations Before and After the Development of Hypertension in SHR

Cited by 88 publications

References 0 publications

Selective Mineralocorticoid Receptor Blocker Eplerenone Reduces Resistance Artery Stiffness in Hypertensive Patients

Selective Mineralocorticoid Receptor Blocker Eplerenone Reduces Resistance Artery Stiffness in Hypertensive Patients

Functional alterations of mesenteric small resistance arteries in Milan hypertensive and normotensive rats

Microcirculation in Hypertension

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