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Results for “Endothelial function”

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PubMed1999

Effect of short- and long-term heart failure on small artery morphology and endothelial function in the rat.

Chronic heart failure (HF) is associated with hemodynamic changes and activation of several neurohormonal systems, which are able both to inhibit and to facilitate arterial growth or remodeling and also to influence endothelial function. As these vascular changes may depend on the duration of HF, we evaluated morphologic and endothelial functional alterations in a rat model of HF after a short and long duration of HF. Rats with coronary ligation and sham-operated controls were investigated either 8 or 26 weeks after the operation with measurements of hemodynamics and isolated mesenteric small artery morphology and endothelial function. The effect of HF and duration of HF were examined by using two-way analysis of variance (ANOVA). HF rats had altered hemodynamics with reductions in cardiac output, left ventricular systolic pressure, and mean blood pressure, whereas left ventricular diastolic pressure was increased. HF caused remodeling of anatomically well-defined mesenteric small arteries with a reduction in media thickness and media-to-lumen ratio, but without change in the media cross-sectional area. Neither HF nor time had any influence on sensitivity or maximal relaxation to acetylcholine in the presence of indomethacin, but HF reduced vasoconstriction due to nitric oxide synthase blockade with N(G)-nitro-L-arginine independent of time. Our results indicate that HF, induced by coronary ligation in the rat, has a remodeling effect on mesenteric small arteries. However, the remodeling is moderate compared with that observed in hypertension. Furthermore, our results suggest that HF reduces basal release of NO.

Acetylcholine↗

PubMed1999

Improvement in endothelial function by angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus.

OBJECTIVES: The aim of this study was to assess the effect of angiotensin-converting enzyme (ACE) inhibition with enalapril on forearm endothelial function in subjects with type II diabetes mellitus. BACKGROUND: Endothelial function is depressed in the presence of conventional risk factors for atherosclerosis, and various therapies, such as lipid-lowering therapy in hypercholesterolemia, can improve endothelial-mediated vasodilation. ACE inhibition has improved such function in several conditions including type I diabetes, but there is no evidence for a beneficial effect in type II diabetes. METHODS: The influence of enalapril (10 mg twice daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 10 type II diabetic subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gage plethysmography and graded intrabrachial infusion of acetylcholine (ACh), N(G)-monomethyl-L-arginine (LNMMA) and sodium nitroprusside (SNP). RESULTS: Enalapril increased the response to the endothelium-dependent vasodilator, ACh (p < 0.02) and the vasoconstrictor response to the nitric oxide (NO) synthase inhibitor, LNMMA (p < 0.002). No difference was evident in the response to SNP. CONCLUSIONS: In type II diabetic subjects without evidence of vascular disease, the ACE inhibitor enalapril improved stimulated and basal NO-dependent endothelial function. The study extends the spectrum of beneficial effects demonstrated to result from ACE inhibition in diabetes.

Acetylcholine↗

PubMed2005

Insulin sensitivity and endothelial function in hypertension: a comparison of temocapril and candesartan.

BACKGROUND: Recent studies have suggested that angiotensin-converting enzyme inhibitors (ACEi) have a more pronounced effect on endothelial function (END) than angiotensin II receptor blocker (ARB); however, whether this pronounced effect is more beneficial to patients with insulin sensitivity (IS) remains uncertain. The present study compared the effects of ACEi and ARB on END and IS in patients with hypertension. METHODS: A total of 23 patients with hypertension were given either ACEi or ARB alternatively in a cross-over manner for 8-week intervals. Both END and IS were examined after each treatment period; END was assessed by the response of forearm blood flow to reactive hyperemia and IS by an insulin tolerance test. The plasma levels of bradykinin (BK), NOx, tumor necrosis factor (TNF-alpha), and adiponectin (Adi) were also measured after each treatment. RESULTS: We found that END, BK, and NOx were higher after the ACEi treatment than after the ARB treatment. Although the IS and the Adi levels were similar after both treatments, the TNF-alpha level was lower after the ARB treatment than after the ACEi. CONCLUSIONS: We conclude that ACEi and ARB may have similar effects on insulin sensitivity, irrespective of the more pronounced effects of ACEi on endothelial function. The BK-NO pathway might contribute, at least in part, to the pronounced effect of ACEi. On the other hand, the underlying mechanisms affecting insulin sensitivity might differ for both treatments. These results suggest that endothelial function is not a major determinant of insulin sensitivity under physiologic conditions.

Angiotensin II Type 1 Receptor Blockers↗

PubMedDate not supplied

Endothelial function in hypertension.

Endothelial dysfunction has been documented both in the forearm and coronary beds of essential hypertensive patients. Impairment in the tonic release of nitric oxide (NO) is secondary to hypertension, while the alteration in agonist-induced endothelium-dependent vasodilation seems to be a primary defect caused both by an alteration of the L-arginine-NO pathway and the production of cyclooxygenase-dependent EDCFs, such as prostanoids or superoxide anions. These latter substances curtail endothelium-dependent vasodilation mainly by inactivating NO production. Although experimental data clearly indicate that the L-arginine-NO pathway participates in the regulation of renal hemodynamics and renal excretory function under basal and stimulated conditions, data in humans are scanty and confounded by methodological approaches. A posteriori interpretation of data obtained with intrarenal infusion of acetylcholine in kidney donors suggests that endothelium dependent vasodilation in the kidney is impaired by aging, a phenomenon well documented in the forearm and coronary circulation. Systemic infusion of L-arginine induced renal vasodilation and natriuresis in normotensive subjects, an effect which seems to be mediated mainly by intrarenal NO production. Moreover the few available data suggest that both renal vasodilation and renal production of NO in response to L-arginine are blunted in patients with essential hypertension and that superoxide anions, may be, at least partially, responsible for this alteration of the L-arginine-NO pathway. In conclusion, endothelial dysfunction has been well documented in the forearm and coronary circulation of patients with essential hypertension. Available data suggest that endothelial, dysfunction is also detectable in the kidney and that a common mechanism, probably superoxide anions, can account for this abnormality.

Arginine↗

PubMed2001

Atrial fibrillation impairs endothelial function of forearm vessels in humans.

BACKGROUND: Although there have been many studies on the effects of atrial fibrillation (AF) on cardiac function, few studies have been done on its effects on endothelial function. The present study was designed to examine the effects of AF on endothelial function in human subjects. METHODS AND RESULTS: Changes in forearm blood flow (FBF) induced by acetylcholine and nitroglycerin were measured by using plethysmography in 14 patients with lone AF, 13 patients with AF and underlying heart disease, and 12 normal control subjects. In the patients, these measurements were repeated after cardioversion. Although baseline FBF was the same in the 3 groups, acetylcholine-induced increases in FBF were significantly smaller in both patient groups than in the control group, and FBF increases were particularly depressed in AF patients with underlying heart disease. After restoration of sinus rhythm by cardioversion, FBF response to the highest dose of acetylcholine increased by 46% in patients with lone AF (n = 10) and by 90% in AF patients with underlying heart disease (n = 11). Nitroglycerin-induced vasodilatation was the same in all 3 groups and was not affected by cardioversion. CONCLUSIONS: These findings suggest that endothelium-dependent vasodilatation is impaired by AF and improves after sinus rhythm is restored.

Acetylcholine↗

PubMed2026

Guidelines for evaluating endothelial function in vascular tissue.

The endothelium plays a central role in maintaining vascular homeostasis by orchestrating vascular tone, inflammation, healing, permeability, and thrombosis. Assessing endothelial function in vascular tissue is essential for understanding the cellular and molecular mechanisms underlying cardiovascular physiology and pathology. Traditional approaches, such as wire and pressure myography, have been instrumental in defining endothelium-dependent responses and identifying key pharmacological targets. However, the complexity and heterogeneity of endothelial cells across vascular beds and their dynamic phenotypic changes in health and disease necessitate the incorporation of new investigative strategies. Emerging methodologies, including bulk and single-cell transcriptomics, proteomics, and advanced imaging, now provide unprecedented insights into endothelial cell diversity and function. A team of leading experts in the field, who collectively reached a consensus on the most widely used techniques to evaluate endothelial function, developed these guidelines. The document establishes best practices for assessing endothelial function, from endothelial cell cultures to isolated vascular tissues, integrating conventional functional assays with modern molecular approaches. By fostering methodological consistency and embracing innovation, our goal is to enhance rigor, reproducibility, understanding, and discovery in endothelial biology.

Humans↗

PubMed2002

Effect of azithromycin treatment on endothelial function in patients with coronary artery disease and evidence of Chlamydia pneumoniae infection.

BACKGROUND: It has been suggested that infection with Chlamydia pneumoniae(CPn) can trigger inflammatory mechanisms that may in turn impair vascular endothelial function. The aim of the present study was to assess whether treatment with the macrolide antibiotic azithromycin improves endothelial function in patients with coronary artery disease and antibodies positive to CPn. METHODS AND RESULTS: We carried out a randomized, prospective, double-blind, placebo-controlled trial in 40 male patients (mean age, 55+/-9 years) with documented coronary artery disease and positive CPn-IgG antibody titers. After baseline evaluation, patients were randomized to receive either azithromycin or placebo for 5 weeks. Flow-mediated dilation (FMD) of the brachial artery and E-selectin, von Willebrand factor, and C-reactive protein (CRP) levels were assessed at study entry and at the end of the treatment period. Our results showed that patients who received azithromycin had a significant improvement in FMD (mean change, 2.1+/-1.1%; P<0.005). In contrast, FMD was not significantly changed in the placebo group (mean change, -0.02+/-0.2%, P=0.64). Azithromycin therapy also resulted in a significant decrease of E-selectin and von Willebrand factor levels. CRP levels were not significantly altered by treatment with either azithromycin or placebo. Beneficial effects of azithromycin treatment were independent from the presence of low (<1:32) or high (> or =1:32) CPn antibody titers. CONCLUSIONS: Our findings indicate that treatment with azithromycin has a favorable effect on endothelial function in patients with documented coronary artery disease and evidence of CPn infection irrespective of antibody titer levels. Whether these favorable actions of antibiotic treatment will translate into a beneficial effect on atherogenesis and cardiac events needs further investigation.

Anti-Bacterial Agents↗

PubMed2004

Does the endothelial function change in renal transplant patients with longer duration of exposure and with higher cumulative doses of cyclosporine?

OBJECTIVE: Administration of cyclosporine (CsA) is one potential cause of endothelial dysfunction in renal transplant patients. We sought to investigate endothelial functional changes with respect to the cumulative dose and duration of exposure to CsA. METHODS: Sixty-six renal recipients and 25 healthy controls were included in the study. The recipients were classified according to their time of CsA exposure: group 1 (0 to 36 months); group 2 (36 to 72 months); and group 3 (over 72 months). Endothelial function of the brachial artery was evaluated using high-resolution vascular ultrasound. Endothelium-dependent and -independent vasodilatation (EDD and EID, respectively) were assessed by assessing the responses to reactive hyperemia and using sublingual isosorbide dinitrate (ISDN), respectively. RESULTS: There were no statistically significant differences between the groups with regard to their demographic, clinical, and most biochemical characteristics. Baseline measurements of the diameter of the brachial artery were similar in all groups. The values of mean brachial artery EDD and EID responses in groups 1, 2, and 3 were less than those in the control group (P < .05, P < .05, and P < .05, respectively). Mean brachial artery EDD and EID in group 1 were significantly impaired compared to groups 2 and 3 (for EDD: P < .05 and P < .05, respectively; for EID: P < .05 and P < .05, respectively). In contrast there was no difference between groups 2 and 3 with respect to these parameters. There were mild to moderate positive correlations between the cumulative doses of CsA and EDD and EID (r = .26 and r = .52, P < .05, respectively). CONCLUSION: Endothelial dysfunction was more prominent in the first 36-month period than later despite the longer exposure to and higher cumulative doses of CsA. This finding may reflect an extended effect of the uremic state on endothelial function or more intense doses of CsA in early posttransplant period.

Adult↗

PubMed2006

Measuring endothelial function.

Dysfunction of the endothelium and of the arterial wall is well described in patients with atherosclerosis, diabetes, and other risk factors for vascular disease. In recent years, clinical research has focused on elucidating the role of this dysfunction in influencing vascular disease progression. Alteration in the structure of arteries and disruption of the homeostatic functions of the endothelium act as a substrate for end-organ damage and the occurrence of vascular events. Dysfunction of the vascular endothelial cells is probably the earliest event promoting atherosclerotic lesion formation. Therefore, methods capable of assessing endothelial function at a preclinical stage hold potential to refine cardiovascular risk stratification and serve as a guide to monitor the effects of therapeutic interventions. A number of methodologies are currently employed to assess endothelial function, but the optimal approach is not firmly established. In this article, we critically appraise the use of different methodologies employed to study endothelial function as a surrogate marker of future cardiovascular risk.

Blood Flow Velocity↗

PubMed1999

Nifedipine improves endothelial function in hypercholesterolemia, independently of an effect on blood pressure or plasma lipids.

OBJECTIVE: Dihydropyridine calcium antagonists have been shown to retard atherogenesis in animal models and to prevent the development of early angiographic lesions in human coronary arteries. Endothelial dysfunction is an early event in the pathogenesis of cardiovascular disease. We investigated whether nifedipine could improve endothelial function in hypercholesterolemia, independently of changes in blood pressure or plasma lipids. METHODS: First, we compared in vivo forearm vascular responses to the endothelium-dependent and independent vasodilators serotonin (5-HT) and sodium nitroprusside (SNP) in 11 patients with familial hypercholesterolemia before and after 6-weeks treatment with nifedipine GITS (60 mg, OD) and in 12 matched controls. In a subgroup of six control subjects forearm vascular function was also assessed before and after 6-weeks nifedipine GITS treatment. In vitro, we subsequently explored possible mechanisms underlying the effect of nifedipine on endothelial function. We investigated the effects of nifedipine on both NO production by recombinant endothelial NO synthase (eNOS) and endothelial cells, using 3H-arginine conversion, as well as on superoxide generation by endothelial cell lysates, using lucigenin enhanced chemiluminescence. RESULTS: In hypercholesterolemia 5-HT-induced vasodilation was impaired (47 +/- 9% increase in forearm bloodflow vs. 99 +/- 8% in controls). Treatment with nifedipine completely restored 5-HT-induced vasodilation (113 +/- 13%), whereas it did not influence basal forearm vasomotion or SNP-induced vasodilation. Nifedipine did not alter forearm vascular responses in control subjects and did not alter blood pressure or plasma lipids. In vitro, we found no direct effect of nifedipine on NO production by recombinant eNOS or endothelial cells. However, we did observe a reduction in endothelial superoxide generation. CONCLUSIONS: Our data show that nifedipine improves endothelial function in hypercholesterolemia. It is suggested from our in vitro experiments that this effect is due to reduced NO degradation.

Adult↗

PubMed2004

Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease.

GLP-1 stimulates insulin secretion, suppresses glucagon secretion, delays gastric emptying, and inhibits small bowel motility, all actions contributing to the anti-diabetogenic peptide effect. Endothelial dysfunction is strongly associated with insulin resistance and type 2 diabetes mellitus and may cause the angiopathy typifying this debilitating disease. Therefore, interventions affecting both endothelial dysfunction and insulin resistance may prove useful in improving survival in type 2 diabetes patients. We investigated GLP-1's effect on endothelial function and insulin sensitivity (S(I)) in two groups: 1) 12 type 2 diabetes patients with stable coronary artery disease and 2) 10 healthy subjects with normal endothelial function and S(I). Subjects underwent infusion of recombinant GLP-1 or saline in a random crossover study. Endothelial function was measured by postischemic FMD of brachial artery, using ultrasonography. S(I) [in (10(-4) dl.kg(-1).min(-1))/(muU/ml)] was measured by hyperinsulinemic isoglycemic clamp technique. In type 2 diabetic subjects, GLP-1 infusion significantly increased relative changes in brachial artery diameter from baseline FMD(%) (3.1 +/- 0.6 vs. 6.6 +/- 1.0%, P < 0.05), with no significant effects on S(I) (4.5 +/- 0.8 vs. 5.2 +/- 0.9, P = NS). In healthy subjects, GLP-1 infusion affected neither FMD(%) (11.9 +/- 0.9 vs. 10.3 +/- 1.0%, P = NS) nor S(I) (14.8 +/- 1.8 vs. 11.6 +/- 2.0, P = NS). We conclude that GLP-1 improves endothelial dysfunction but not insulin resistance in type 2 diabetic patients with coronary heart disease. This beneficial vascular effect of GLP-1 adds yet another salutary property of the peptide useful in diabetes treatment.

Adult↗

PubMed2000

Lipoprotein (a) is associated with endothelial function in healthy postmenopausal women.

BACKGROUND: Lipoprotein (a) (Lp(a)) is an independent risk factor for atherosclerotic cardiovascular disease. The atherogenic potential of Lp(a) may be by impairment of endothelial function. Objectives. We investigated the relation of Lp(a) plasma levels to endothelium dependent and independent dilatation of the brachial artery in healthy postmenopausal women. METHODS: One hundred and five healthy postmenopausal women aged 52-67 years were included in the study. Endothelial function was assessed non-invasively by measuring percent lumen diameter change in the brachial artery after reactive hyperemia and sublingual nitroglycerine spray. RESULTS: Flow mediated dilatation was inversely related to the plasma logLp(a) level. Mean change per unit logLp(a) increase:-2.83% (95% CI: -5.22--0.43). Elevated Lp(a) (>239 mg/l) (upper quartile) was associated with an impaired flow mediated vasodilatation (2.4%+/-1. 2) compared to Lp(a) < or =239 mg/l (5.2%+/-0.7). Adjustment for other cardiovascular risk factors did not change the magnitude of the association. Nitroglycerine-induced vasodilatation was not significantly lower in the high Lp(a) level group, compared to the group with normal levels of Lp(a) (< or =239 mg/l) (8.0+/-1.2 vs. 11.4%+/-0.8). CONCLUSION: Elevated lipoprotein (a) levels are associated with an impaired endothelial function in healthy postmenopausal women, independent of conventional risk factors for cardiovascular disease. Since Lp(a) may be pathogenetically important for early vascular damage, elevated Lp(a) levels might contribute to the increased cardiovascular risk seen in postmenopausal women.

Administration, Sublingual↗

PubMed2006

Impaired endothelial function in patients with myocardial bridge.

OBJECTIVE: The relationship between myocardial bridging (MB) and ischemic heart disease is still controversial. In this study, we aimed to evaluate the existing atherosclerosis and noninvasive endothelial function of brachial artery in patients with MB. METHODS: The present study included 50 patients (group I) who had MB in left anterior descending (LAD) on coronary angiography. All of the coronary artery segments were evaluated by intravascular ultrasound (IVUS). Endothelial function was assessed with measurement of flow-mediated dilatation (FMD) and nitrate-dependent dilatation in the brachial artery. The study also included 30 healthy control subjects (group II). Patients in the group I were further subdivided into two subgroups based on the findings on IVUS: group IA included 20 patients without atherosclerotic lesions and group IB included 30 patients with atherosclerotic coronary artery disease in addition to MB. RESULTS: FMD values were found to be significantly lower in the patients with MB (group I) than in the control (6.4 +/- 3% vs 11 +/- 4%, P <0.001). In regard to FMD values in subgroups, FMD was 7 +/- 2% in the group IA and 5.8 +/- 1% in the group IB (P = 0.023). On IVUS, atherosclerotic plaque was found proximal to the bridge in the same coronary artery segment in addition to MB in 75% of the patients in group I (group IB). No atherosclerotic plaque was found in within or distal segments of MB. CONCLUSION: Endothelial function is impaired in patients with MB and there is an increased tendency for atherosclerosis proximal to the bridge in the patients with MB. Endothelial dysfunction is more severe in the patients with atherosclerosis proximal to the bridge.

Administration, Sublingual↗

PubMed2006

Effect of postconditioning on coronary blood flow velocity and endothelial function and LV recovery after myocardial infarction.

OBJECTIVE: Postconditioning is a novel approach to myocardial protection during ischemia reperfusion. Our study observed the effect of postconditioning on coronary blood flow velocity and endothelial function in patients who underwent emergency percutaneous coronary intervention (PCI). METHODS: Ninety-four patients with their first acute myocardial infarction who underwent revascularization within 12 hours of onset by primary PCI were recruited in the study. All the patients were randomized to two groups, IR group (PCI without postconditioning) and Postcond group (PCI with postconditioning). Corrected TIMI frame count (CTFC) was used to evaluate velocity of coronary blood after PCI. Creatine phosphokinase (CK), CK-MB, and malondialdehyde (MDA) were measured before and after PCI. Arterial endothelial function was studied noninvasively by examination of brachial artery responses to endothelium-dependent and endothelium-independent stimuli by echo Doppler technique. Wall motion score index (WMSI) was assessed by two-dimensional echocardiography before and 8 weeks after angioplasty. RESULTS: There were no significant differences between the two groups with regard to age, sex, presence of angiographically visible collaterals, and elapsed time from the onset of symptoms until perfusion. Patients with postconditioning had much faster CTFC than patients without postconditioning (25.38 +/- 5.35 vs 29.23 +/- 5.54). After 8 weeks, the WMSI improved significantly in both groups, but the DeltaWMSI in Postcond group was significantly larger than that of IR group (1.20 +/- 0.30 vs 1.04 +/- 0.36, P < 0.05). There was a significant negative correlation between DeltaWMSI and CTFC in IR group and Postcond group (r = -0.9032, P < 0.01; r = -0.7884, P < 0.01). The peaks of CK and CK-MB of Postcond group were much lower than that of IR group (1236.57 +/- 813.21 U/L vs 1697.36 +/- 965.74 U/L; 116.92 +/- 75.83 U/L vs 172.41 +/- 92.64 U/L), and MDA-reactive products were significantly lower than that in the IR group at any same time after PCI. All patients with acute myocardial infarction had a depressed endothelium-dependent vasodilation function, while the endothelium-dependent vasodilation function was improved in Postcond group. CONCLUSION: Postconditioning is a simple, operative procedure for salvaging the coronary endothelial function and cardiomyocyte. It could be used widely in clinic and to better the prognosis of acute myocardial infarction.

Aged↗

PubMed1996

Arterial bypass graft spasm: an examination of the role of high flow demands and endothelial function in the porcine GEA.

This study examined why an artery becomes vulnerable to spasm when used as a bypass graft. We hypothesized that high flow demands would decrease pressure distally in the conduit (afterload), thus increasing the sensitivity to vasoconstrictors. Furthermore, perioperative endothelial dysfunction would additionally sensitize the artery to constrictors. Six gastroepiploic arteries (GEA, 1.0-1.5 mm diameter, 11 cm length) were harvested from adult pigs (110-125 kg) and mounted on a computer-controlled perfusion system. The inflow pressure was set at 80 mmHg and outflow resistance was adjusted to simulate normal (in situ) or high (coronary bypass graft) flow demands. Gastroepiploic flow and distal pressures were measured at baseline [B] and after adding norepinephrine (NE, 10(-9) M to 10(-5) M). Under normal flow demand, a minimal pressure drop existed across the GEA and flow decreased only at high NE concentrations. High flow demand decreased distal GEA pressure and increased the sensitivity to NE. To block endothelial function N-Monomethyl-L-Arginine, Monoacetate (L-NMMA, 10(-5) M) was then added. Under high flow demand, blocking endothelial function resulted in an additional fivefold increase in sensitivity to NE (ED50 from 9.75 10(-8) M to 2.11 10(-8) M, P < 0.05). It was shown that in long narrow arterial grafts, high flow demands cause cumulative pressure losses. Even with normal endothelial function, these pressure losses render the artery responsive to vasoconstrictors. Endothelial dysfunction additionally increases the sensitivity of the artery. Anastomosis of a small arterial graft to a large myocardial perfusion bed may result in reduced distal conduit pressure and may predispose to the development of myocardial ischemia even when low doses of vasoconstrictors are used. Perioperative endothelial dysfunction may exacerbate this effect.

Abdominal Muscles↗

PubMed2003

Potential mechanisms of impaired endothelial function in arterial hypertension and hypercholesterolemia.

This review focuses on the role of impaired endothelial function for the development of atherosclerosis in human arterial hypertension and hypercholesterolemia in vivo. Potential mechanisms underlying impaired endothelial function and decreased bioavailability of nitric oxide under these clinical conditions are discussed. It further addresses therapeutic strategies aimed at improving the bioavailability of nitric oxide in these patients. The overall conclusion is that the bioavailability of nitric oxide is probably impaired, not by a single defect, but by various mechanisms affecting nitric oxide synthesis as well as nitric oxide breakdown. In both diseases increased superoxide anion production and oxidative stress represent a major mechanism. Decreased bioavailability of nitric oxide not only impairs endothelium-dependent vasodilation, but also activates other mechanisms that play an important role in the pathogenesis of atherosclerosis. Thus, therapeutic strategies should aim to restore bioavailability of nitric oxide, which has been demonstrated for lipid-lowering therapy in hypercholesterolemia and blood pressure control in hypertension. In addition, antioxidative strategies will represent a major therapeutic tool against atherosclerotic diseases in the future. Statins and blockers of the renin-angiotensin system seem to have such antioxidative effects independent from their effects on lipid profiles or blood pressure control.

Animals↗

PubMed2003

Endothelial function, inflammation, and prognosis in cardiovascular disease.

The vascular endothelium is an active, dynamic tissue that controls many important functions, including regulation of vascular tone and maintenance of blood circulation, fluidity, coagulation, and inflammatory responses. Cardiovascular risk factors affect many of the normal functions of the endothelium. In particular, oxidized low-density lipoprotein cholesterol initiates a series of events that begin with cell activation, endothelial dysfunction, local inflammation, and a procoagulant vascular surface. These conspire to result in plaque formation and ultimately plaque rupture and cardiovascular events. Endothelial dysfunction may be evaluated by means of invasive techniques, such as coronary artery reactivity to acetylcholine, or noninvasive techniques, such as brachial artery ultrasonography. Loss of endothelium-dependent vasodilation is a characteristic feature throughout the development of atherosclerosis, and it is independently related to future adverse cardiovascular risk. Therefore, measurement of endothelial function can possibly be used to determine risk, to triage management, and to improve outcomes. At the same time, inflammation is a crucial factor in the atherosclerotic disease process. To identify and monitor the ongoing inflammatory process, markers of inflammation such as C-reactive protein (CRP) have been studied. Scientific evidence shows that elevated plasma CRP values add to the predictive ability of other established risk factors; moreover, elevated values appear to augment the Framingham Coronary Risk Score in identifying individuals who should be considered for cardioprotective treatment programs. Interestingly, thiazolidinediones (TZDs), peroxisome proliferator-activated receptor-gamma agonists that are effective in the treatment of type 2 diabetes mellitus, not only increase insulin sensitivity but can benefit endothelial function because they exhibit anti-inflammatory effects. For many individuals, including those with the metabolic syndrome and/or type 2 diabetes, endothelial dysfunction and elevated plasma CRP levels indicate increased risk of cardiovascular disease. Notably, the TZDs have been shown to reduce CRP levels and may improve endothelial function.

Cardiovascular Diseases↗

PubMed2003

Effects of dietary supplementation with isoflavones from red clover on ambulatory blood pressure and endothelial function in postmenopausal type 2 diabetes.

OBJECTIVE: The aim of this study was to determine whether dietary supplementation with isoflavones from red clover affected ambulatory blood pressure and forearm vascular endothelial function in postmenopausal type 2 diabetic women. DESIGN: Sixteen postmenopausal type 2 diabetics treated with diet or oral hypoglycaemic therapy completed a randomized double-blind crossover trial of dietary supplementation with isoflavones from red clover (approximately 50 mg/day) for 4 weeks compared to placebo. Twenty-four-hour ambulatory blood pressure recordings and forearm vascular responses to acetylcholine, nitroprusside and L-nitromonomethylarginine (L-NMMA) were measured at the end of each treatment period. RESULTS: Mean daytime systolic and diastolic blood pressures were significantly lower during isoflavone therapy compared to placebo (-8.0 +/- 3.4 and -4.3 +/- 1.9 mmHg respectively, p < 0.05). The increase in forearm vascular resistance following L-NMMA was significantly greater during isoflavone supplementation (20.9 +/- 6.5) than placebo (3.7 +/- 2.9 arbitrary units, p < 0.05), suggesting an improvement in basal endothelial function. Plasma lipoproteins, glycated haemoglobin and forearm vascular responses to acetylcholine and nitroprusside did not differ significantly between isoflavone and placebo therapy. CONCLUSION: Isoflavone supplementation from red clover may favourably influence blood pressure and endothelial function in postmenopausal type 2 diabetic women.

Aged↗