Vasodilatation, not hypotension, improves resistance vessel design during treatment of essential hypertension: a literature survey

Christensen, Kent Lodberg; Mulvany, Michael J.

doi:10.1097/00004872-200106000-00002

Cited by 81 publications

(79 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…23 Vasodilatation under antihypertensive treatment has been implicated to play a role in the correction of vascular remodeling rather than just the lowering of BP. 24,25 Vascular remodeling was not significantly improved in the present study either by eplerenone or atenolol after 1 year of treatment, despite good BP control with both agents. This might, therefore, be explained in part by the fact that neither atenolol nor eplerenone act as a vasodilator agent.…”

Section: Discussioncontrasting

confidence: 68%

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

Nazzaro

Federici

Lucivero

et al. 2007

High Blood Pressure & Cardiovascular Prevention

View full text Add to dashboard Cite

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...

show abstract

Section: Discussioncontrasting

confidence: 68%

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

Nazzaro

Federici

Lucivero

et al. 2007

High Blood Pressure & Cardiovascular Prevention

View full text Add to dashboard Cite

show abstract

“…In this regard, it was proposed that vasodilatation, not hypotension, improves resistance vessel design during treatment of essential hypertension 37 ; therefore, as previously mentioned, the extent of blood pressure reduction during treatment may have a limited role.…”

Section: Discussionmentioning

confidence: 99%

Effects of a Long-Term Treatment With Aliskiren or Ramipril on Structural Alterations of Subcutaneous Small-Resistance Arteries of Diabetic Hypertensive Patients

et al. 2014

View full text Add to dashboard Cite

Abstract-Structural alterations of subcutaneous small-resistance arteries are associated with a worse clinical prognosis in hypertension and non-insulin-dependent diabetes mellitus. The effects of the direct renin inhibitor aliskiren on microvascular structure were never previously evaluated. Therefore, we investigated the effects of aliskiren in comparison with those of an extensively used angiotensin-converting enzyme inhibitor, ramipril, on peripheral subcutaneous small-resistance artery morphology, retinal arteriolar structure, and capillary density in a population of patients with non-insulin-dependent diabetes mellitus. Sixteen patients with mild essential hypertension and with a previous diagnosis of non-insulin-dependent diabetes mellitus were included in the study. Patients were then randomized to 1 of the 2 active treatments (aliskiren 150 mg once daily, n=9; or ramipril 5 mg once daily, n=7). Each patient underwent a biopsy of the subcutaneous fat from the gluteal region, an evaluation of retinal artery morphology (scanning laser Doppler flowmetry), and capillary density (capillaroscopy), at baseline and after 1 year of treatment. Subcutaneous small arteries were dissected and mounted on a pressurized micromyograph, and the media-to-lumen ratio was evaluated. A similar office blood pressure-lowering effect and a similar reduction of the wall-to-lumen ratio of retinal arterioles were observed with the 2 drugs. Aliskiren significantly reduced media-to-lumen ratio of subcutaneous small-resistance arteries, whereas ramipril-induced reduction of media to lumen ratio was not statistically significant. No relevant effect on capillary density was observed. In conclusion, treatment with aliskiren or ramipril was associated with a correction of microvascular structural alterations in patients with non-insulin-dependent diabetes mellitus. An increased media-to-lumen ratio of subcutaneous smallresistance arteries is a potent predictor of cardiovascular events in patients with increased blood pressure values, [10][11][12] part of them being also diabetics.10,11 Antihypertensive treatment is able to regress structural alterations in subcutaneous small-resistance arteries of essential hypertensive patients 13 ; however, despite similar blood pressure-lowering effects, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptors blockers, and calcium channel blockers proved to be more effective than diuretics and β-blockers in terms of reduction in the media-to-lumen ratio. 13 The extent of the reduction in the media-to-lumen ratio of subcutaneous small-resistance arteries was recently demonstrated to be an independent predictor of cardiovascular events in essential hypertension. 14 However, in patients with diabetes mellitus, it seems more difficult to obtain a complete regression of small-resistance artery structural alterations, despite prolonged treatment. 15-18A possible explanation is related to the presence, in patients with diabetes mellitus, of hypertrophic remodeling of small arteries, which repre...

show abstract

“…Remodeling of the vasculature in hypertension involves rearrangement of cellular and extracellular components and has been reviewed extensively. [1][2][3][4][5][6] The present review highlights recent developments in the understanding of cellular and molecular mechanisms underlying increased vasoconstriction in hypertension with an emphasis on the RhoA/Rhokinase signaling pathway in vascular smooth muscle. …”

mentioning

confidence: 99%

Hypertension and RhoA/Rho-Kinase Signaling in the Vasculature

2004

View full text Add to dashboard Cite

Abstract-Under normal conditions, contractile activity in vascular smooth muscle is initiated by either receptor activation (norepinephrine, angiotensin II, etc.) or by a stretch-activated mechanism. After this activation, several signaling pathways can initiate a Ca 2ϩ -calmodulin interaction to stimulate phosphorylation of the light chain of myosin. Ca 2ϩ sensitization of the contractile proteins is signaled by the RhoA/Rho-kinase pathway to inhibit the dephosphorylation of the light chain by myosin phosphatase thereby maintaining force generation. In opposition to force generation, NO is released from endothelial cells and causes vasodilation through inhibition of the RhoA/Rho-kinase signaling pathway. This brief review will highlight recent studies demonstrating a role for the RhoA/Rho-kinase signaling pathway in the increased vasoconstriction characteristic of hypertension. Key Words: vasculature Ⅲ signal transduction Ⅲ muscle, smooth Ⅲ nitric oxide Ⅲ vasoconstriction I ncreased peripheral vascular resistance causes elevated arterial pressure in hypertension. Arterial wall thickening, increased vasoconstriction, and reduced vasodilation contribute to this increased peripheral resistance. Multiple regulatory processes (neural, humoral, etc.) and complex cell signaling pathways modulate vascular smooth muscle cell (VSMC) contraction, relaxation, and growth. Under normal conditions, these regulatory processes maintain vessel wall integrity and do not contribute to pathological increases in blood pressure. Remodeling of the vasculature in hypertension involves rearrangement of cellular and extracellular components and has been reviewed extensively. [1][2][3][4][5][6] The present review highlights recent developments in the understanding of cellular and molecular mechanisms underlying increased vasoconstriction in hypertension with an emphasis on the RhoA/Rhokinase signaling pathway in vascular smooth muscle. Contractile MechanismVascular smooth muscle contraction is principally regulated by receptor and mechanical (stretch) activation of the contractile proteins. 7 Depolarization of the plasma membrane can also trigger contraction. For contraction to occur, myosin light chain (MLC) kinase must phosphorylate the light chain of myosin, enabling the cycling of myosin cross-bridges with actin. 7-9 Thus, contractile activity is determined primarily by the phosphorylation state of the light chain of myosin. 8,9 In VSMCs of some blood vessels, phosphorylation of the light chain of myosin is maintained at a low level in the absence of external stimuli (ie, no receptor or mechanical activation). This activity results in what is known as myogenic tone.Recent work suggests that 20-HETE may play a signaling role in the myogenic response of pig coronary arteries. Randriamboavonjy et al 10 observed that 20-HETE elicited contraction and phosphorylation of the light chain of myosin. Both of these activities were inhibited by Y-27632, a Rhokinase inhibitor (see below for description of signaling pathway). Ca 2؉ -Dependent Con...

show abstract

Vasodilatation, not hypotension, improves resistance vessel design during treatment of essential hypertension: a literature survey

Cited by 81 publications

References 48 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

Effects of a Long-Term Treatment With Aliskiren or Ramipril on Structural Alterations of Subcutaneous Small-Resistance Arteries of Diabetic Hypertensive Patients

Hypertension and RhoA/Rho-Kinase Signaling in the Vasculature

Contact Info

Product

Resources

About