Effects of Angiotensin Type-1 Receptor Antagonism on Small Artery Function in Patients With Type 2 Diabetes Mellitus

Malik, Rayaz A.; Schofield, Ian; Izzard, Ashley S.; Austin, Clare; Bermann, Georgina; Heagerty, AM

doi:10.1161/01.hyp.0000153305.50128.a1

Cited by 47 publications

(41 citation statements)

References 39 publications

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“…Blood pressure was higher in control participants, but this was not significant, and, indeed, the structural pattern of wall growth traditionally associated with hypertension was observed in depressed patients. Treatment with angiotensin-converting enzyme inhibitors or calcium channel blockers, which are known to influence small artery endothelial function 21 or wall remodeling, [22][23][24] was similar between the 2 groups of patients studied. Depressed patients were more likely to be taking statins, which can improve small artery endothelial function, 25 but despite this, relaxation to acetylcholine was impaired compared with control participants.…”

Section: Discussionmentioning

confidence: 76%

“…Small arteries 100 to 150μm in diameter were dissected from the tissue and carefully cleaned under a dissecting microscope. Isolated vessels were then transferred to an arteriographic bath chamber (Living systems Instrumentation) and cannulated as described previously 21 . The chamber was placed on the stage of an inverted microscope and superfused with PSS, gassed with 5% CO 2 /95% air (pH 7.4 to 7.45) at 37°C, at a superfusion rate of 20mL/min.…”

Section: Gluteal Fat Biopsymentioning

confidence: 99%

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Cerebrovascular Damage in Late-Life Depression Is Associated With Structural and Functional Abnormalities of Subcutaneous Small Arteries

et al. 2010

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Abstract-Late-life depression is increasingly viewed as a vascular illness because of patients exhibiting characteristic white matter brain lesions and in vivo large artery endothelial dysfunction. However, the "vascular depression" hypothesis pertains to the microvasculature, and this circulation has not been studied in this context. Our objective was to examine structure and function of small subcutaneous arteries in patients with late-life depression. Thus, 16 patients aged 71.8Ϯ4.0 years with late-life depression were compared with 15 control participants aged 72.1Ϯ5.9 years. There were similar cardiovascular profiles between the 2 groups. All of the participants underwent MRI brain scans and subcutaneous gluteal fat biopsy from which small arteries were isolated and studied using pressure myography. Cerebral microvascular damage in depressed patients was confirmed by assessment of basal ganglia Virchow-Robin space scores (depressed patients 3.9Ϯ1.7 versus controls: 2.5Ϯ1.6; Pϭ0.01). Contractility to norepinephrine was equivalent in both groups, but relaxation of the small arteries to acetylcholine was significantly reduced in depressed patients (84.0Ϯ4.0%) compared with control participants (96.0Ϯ1.4%; Pϭ0.012). This difference in arterial relaxation was reduced but not entirely eliminated when NO synthase was inhibited. Depressed patients also exhibited hypertrophic wall growth with an increase in medial cross-sectional area (Pϭ0.035, multiple ANOVA and wall thickness; Pϭ0.04, multiple ANOVA).In conclusion, despite similar cardiovascular profiles, depressed patients with cerebral microvascular damage show abnormalities of subcutaneous small artery structure and function. (Hypertension. 2010;56:734-740.)

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Section: Discussionmentioning

confidence: 76%

Section: Gluteal Fat Biopsymentioning

confidence: 99%

Cerebrovascular Damage in Late-Life Depression Is Associated With Structural and Functional Abnormalities of Subcutaneous Small Arteries

et al. 2010

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“…The improvement of acetylcholine-mediated vascular relaxation may be due to increased formation of NO capable of overcoming quenching by superoxide and/or improved formation/ activity of endothelium-derived hyperpolarizing factor. [79][80][81] In this regard, Kihara et al 82 have demonstrated that treatment of diabetic rats with ACEis improves diabetic neuropathy by increasing NO synthase synthesis.…”

Section: Diabetic Neuropathymentioning

confidence: 99%

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

2009

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Since their inception, angiotensin-converting enzyme (ACE) inhibitors have been used as first-line therapy for the treatment of cardiovascular and renal diseases. They restore the balance between the vasoconstrictive salt-retentive and hypertrophy-causing peptide angiotensin II (Ang II) and bradykinin, a vasodilatory and natriuretic peptide. As ACE is a promiscuous enzyme, ACE inhibitors alter the metabolism of a number of other vasoactive substances. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have been proven effective in the treatment of hypertension, and reduce mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction. They inhibit ischemic events and stabilize plaques. Furthermore, they delay the progression of diabetic nephropathy and neuropathy and act as antioxidants. Ongoing studies have elucidated protective roles for them in both memory-related disorders and cancer. INTRODUCTIONIn recent years, stressful and fiercely competitive lifestyles and food habits have compounded the problems of hypertension. Long-standing and stressful, progressively rising hypertension can lead to many disorders, including myocardial infarction (MI), cerebrovascular events, congestive heart failure, peripheral arterial insufficiency, premature mortality 1 and renal dysfunction leading to glomerulosclerosis and kidney artery aneurysm. 2 A number of therapies are available, but angiotensin-converting enzyme (ACE) inhibitors have been the preferred first-line therapy for hypertension, congestive heart failure, left ventricular (LV) systolic dysfunction and MI. 3,4 ACE inhibitors (ACEis) have been in use for the past two decades, and the interest in them is still growing. Recently, the discovery of domain-selective ACEis and new members of the renin-angiotensin system (RAS) (that is, angiotensin-converting enzyme 2) have again fueled the interest of researchers. Some new studies have expanded the already impressive clinical profile of ACEis. This review traces some already known and new facets of ACE inhibition and introduces new advances in the designing of a new generation of ACEis.

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“…Glycated hemoglobin, free radicals, and oxidized low-density lipoproteins also quench the effect of NO. In diabetics, autonomic autoregulation is impaired as shown by the deficient endotheliumdependent relaxation to acetylcholine and bradykinin (Malik et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Mean arterial pressure nonlinearity in an elastic circulatory system subjected to different hematocrits

Branigan

Bolster

Vázquez

et al. 2010

Biomech Model Mechanobiol

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The level of hematocrit (Hct) is known to affect mean arterial pressure (MAP) by influencing blood viscosity. In the healthy population, an increase in Hct (and corresponding increase in viscosity) tends to raise MAP. However, data from a clinical study of type 2 diabetic patients indicate that this relationship is not universal. Instead, individuals in the lower levels of Hct range display a decrease in MAP for a given rise in Hct. After reaching a minimum, this trend is reversed, so that further increases in Hct lead to increases in MAP. We hypothesize that this anomalous behavior occurs due to changes in the circulatory autoregulation mechanism. To substantiate this hypothesis, we develop a physically based mathematical model that incorporates autoregulation mechanisms. Our model replicates the anomalous U-shaped relationship between MAP and Hct found in diabetic patients in the same range of Hct variability.

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Effects of Angiotensin Type-1 Receptor Antagonism on Small Artery Function in Patients With Type 2 Diabetes Mellitus

Cited by 47 publications

References 39 publications

Cerebrovascular Damage in Late-Life Depression Is Associated With Structural and Functional Abnormalities of Subcutaneous Small Arteries

Cerebrovascular Damage in Late-Life Depression Is Associated With Structural and Functional Abnormalities of Subcutaneous Small Arteries

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

Mean arterial pressure nonlinearity in an elastic circulatory system subjected to different hematocrits

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