UMLS:C0020538 - FACTA Search

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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interest in the endothelium has been growing in recent decades and the traditional belief that it provides an inert interface between blood and the vessel wall is no longer the case. It is now clear that the endothelium produces a large number of substances that influence blood flow, and it is in turn affected by changes in the blood and the pressure of blood flow. Nitric oxide and endothelins are the major regulators of the vascular tone, and thereby the blood pressure. Historically speaking, concepts such as endothelial cell damage and injury were described in the 1960s and 1970s. More recently, terms such as endothelial cell activation and dysfunction have also been introduced. Although similar in some respects or part of a continuum, these terms differ in the actual effects on the endothelium, and hence differentiation is important. In hypertension, the delicate balance between the vasodilators and the vasoconstrictors is upset, with disturbance in the nitric oxide pathways that lead to a predominance of the vasoconstrictors. This in turn leads to many other changes that take place in the endothelium, setting up a vicious cycle that maintains the high blood pressure. Therefore, accurate assessment of vascular function is important in linking pathophysiology with clinical disease, such as hypertension. Indeed, there are several methods currently employed experimentally to assess endothelial dysfunction. However, the most widely studied and accepted tests are the estimation of plasma markers such as von Willebrand factor, E-selectin and thrombomodulin, and studies of forearm circulation in response to hypoxia induced stress ('flow mediated dilatation', FMD) or intra arterially administered drugs such as acetyl choline. The present document examines these topics. Whilst acknowledging the debt owed to animal models in the study of hypertension, we shall focus on work where primary study is in homo sapiens. A greater appreciation of how endothelial assessments are made in hypertension will have relevance for drug development and future management strategies.
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PMID:Endothelial dysfunction: methods of assessment and application to hypertension. 1557 56

Elevation of plasma VEGF (vascular endothelial growth factor) has been noted in patients with hypertension or atherosclerosis. VEGF has been regarded as a marker for endothelial dysfunction. However, the role of VEGF in hypertension-induced vascular injury and its relationship with endothelial function have not been studied. This study included 20 untreated hypertensive men with grade 1 or 2 hypertensive retinopathy, 10 untreated hypertensive men without hypertensive retinopathy and 10 healthy controls. None of the hypertensive patients had diabetes, renal impairment or overt vascular diseases. Plasma VEGF and adhesion molecules were measured using ELISAs. Endothelial function was measured by FMD (flow-mediated vasodilation) of the brachial artery. Plasma levels of VEGF, excluding adhesion molecules, were significantly higher in hypertensive patients with retinopathy when compared with patients without retinopathy (152.4+/-80.8 pg/ml versus 104.7+/-27.2 pg/ml, P = 0.035) or controls (152.4+/-80.8 pg/ml versus 98.9+/-23.7 pg/ml, P = 0.025). Levels of FMD were significantly lower in hypertensive patients than controls, but there were no significant differences between patients with or without retinopathy. Degrees of FMD were inversely correlated with VEGF levels (r = -0.351, P = 0.031). Elevation of plasma VEGF was associated with hypertensive retinopathy. Plasma VEGF could be used as a marker of early vascular damage induced by hypertension.
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PMID:Plasma vascular endothelial growth factor as a marker for early vascular damage in hypertension. 1574 Apr 59

The main objective of this study was to assess whether aspirin 100 mg QD can improve blood pressure (BP) control and endothelial function in subjects with arterial hypertension (AH) and hypercholesterolaemia. In total, 21 patients of both sexes (52.1+/-11.5 years) with treated AH and hypercholesterolaemia on antihypertensive and statin therapy were included in the treatment group. In the control group, 20 matched patients of both sexes (51.3+/-12.7 years), but without statin therapy, were recruited. Treatment group subjects received aspirin (100 mg QD) for a duration of 12 weeks at randomization (Treatment phase-1), followed by single blind matching placebo for 12 weeks (Placebo phase) and then again received aspirin (100 mg QD) for an additional 12 weeks (Treatment phase-2). The control group participated in Treatment phase-1, but did not continue Placebo phase and Treatment phase-2. At randomization and at the end of each study phase, mean 24-h systolic BP (SBP) and diastolic BP (DBP) were assessed by 24-h ambulatory blood pressure monitoring (ABPM) and endothelium-dependent (flow mediated, FMD) and -independent (nitroglycerin induced, NTG) vasodilatations of brachial artery were measured using high-resolution ultrasound. In Treatment phase-1, reduction of SBP and DBP (DeltaSBP 5.7+/-2.6 mmHg, P=0.008; DeltaDBP 3.8+/-1.7 mmHg, P=0.014) and improvement of FMD (4.1+/-0.6%, P=0.019), in Placebo phase an elevation of SBP and DBP (DeltaSBP -6.2+/-2.9 mmHg, P=0.002; DeltaDBP -4.2+/-1.9 mmHg, P=0.031) and worsening of FMD (-3.8+/-0.9%, P=0.027), and in Treatment phase-2 reduction of SBP and DBP (DeltaSBP 4.9+/-2.3 mmHg, P=0.005; DeltaDBP 4.1+/-1.3 mmHg, P=0.024) and improvement of FMD (4.5+/-1.3%, P=0.009) were observed in the treatment Group but not in the control group. Addition of low-dose aspirin to antihypertensive medications and statins in hypertensive and hypercholesterolaemic subjects can reduce both SBP and DBP by improvement of endothelial function.
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PMID:Effects of low-dose aspirin on blood pressure and endothelial function of treated hypertensive hypercholesterolaemic subjects. 1590 86

The aim of the study was to evaluate the endothelium dependent FMD of the brachial artery in patients with LVDD. Endothelial function was assessed in 36 male patients (mean age 49+/-6 years) with LVDD due to CAD (22 patients) and essential hypertension (14 patients) as well as in 18 male patients (control group) without LVDD (12 patients with CAD and 6 with hypertension) of matched age. Our studies had showed significant decrease of FMD in patients with LVDD compared to those without LVDD (4.67%+/-1.68 vs. 6.12%+/-2.54, p<0.05). At the same time FMD in both groups appeared to be significantly lower than in healthy subjects. Post-ISDN vasodilation was almost similar in both groups of patients and lower than in controls. The post-ISDN vasodilatation did not differ regarding presence of LVDD or causative disease (CAD or arterial hypertension) and its extent was lower than in healthy controls. A weak correlation was found between FMD and post-ISDN vasodilatation (r=0.231, p>0.05). Data obtained suggest that endothelial dysfunction exists in patients with diastolic dysfunction. Based on these results it is considered that patients with early stages CAD and arterial hypertension depressed FMD might be indicator of LVDD.
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PMID:Flow-mediated dilation in patients with left ventricular diastolic dysfunction. 1636 63

It is assumed that endothelial dysfunction due to arterial hypertension could be improved or even normalized by antihypertensive treatment. The present study was designed to explore that assumption in patients with essential hypertension treated with an angiotensin-converting enzyme (ACE) inhibitor-enalapril. Twenty-eight patients (mean age: 55.1 years) who fulfilled the following criteria were included: essential arterial hypertension present for more than 2 years, monotherapy with enalapril for at least 1 year, adequate treatment (blood pressure in the last year <140/90 mm Hg) and absence of other factors (smoking, hypercholesterolemia, diabetes, obesity), which could importantly influence endothelial function. The flow-mediated (endothelium-dependent) dilation (FMD) of the brachial artery was assessed by high-resolution ultrasound and compared with that of 22 age-matched healthy normotensive controls. The patients and controls did not differ in regard to body mass index, lipids, and plasma glucose and insulin; there were no smokers. FMD of the brachial artery was significantly decreased in patients in comparison to controls (7.9% vs 13.5%, p<0.01). FMD in patients was inversely correlated with the duration of hypertension (r = -0.52, p<0.01) and with both systolic (r = -0.72, p<0.01) and diastolic (r = -0.43, p<0.05) blood pressure (measured after temporary withdrawal of treatment). This study showed that the adequate control of blood pressure achieved with enalapril is not followed by normalization of endothelial function, measured by FMD of the brachial artery.
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PMID:Treatment of essential arterial hypertension with enalapril does not result in normalization of endothelial dysfunction of the conduit arteries. 1651 26

Previous work from our laboratory demonstrated that isometric handgrip (IHG) training improved local, endothelium-dependent vasodilation in medicated hypertensives [McGowan CL (PhD Thesis), 2006; McGowan et al. Physiologist 47: 285, 2004]. We investigated whether changes in the capacity of smooth muscle to dilate (regardless of endothelial factors) influenced this training-induced change, and we examined the acute vascular responses to a single bout of IHG. Seventeen subjects performed four 2-min unilateral IHG contractions at 30% of maximal voluntary effort, three times a week for 8 wk. Pre- and posttraining, brachial artery flow-mediated dilation (FMD, an index of endothelium-dependent vasodilation) and nitroglycerin-mediated maximal vasodilation (an index of endothelium-independent vasodilation) were measured in the exercised arm by using ultrasound before and immediately after acute IHG exercise. IHG training resulted in improved resting brachial FMD (P < 0.01) and no change in nitroglycerin-mediated maximal vasodilation. Pre- and posttraining, brachial artery FMD decreased following an acute bout of IHG exercise (normalized to peak shear rate, pre-, before IHG exercise: 0.01 +/- 0.002, after IHG exercise: 0.008 +/- 0.002%/s(-1); post-, before IHG exercise: 0.020 +/- 0.003, after IHG exercise: 0.010 +/- 0.003%/s(-1); P < 0.01). Posttraining, resting brachial artery FMD improved yet nitroglycerin-mediated maximal vasodilation was unchanged in persons medicated for hypertension. This suggests that the training-induced improvements in the resting brachial artery FMD were not due to underlying changes in the forearm vasculature. Acute IHG exercise attenuated brachial artery FMD, and although this impairment may be interpreted as hazardous to medicated hypertensives with already dysfunctional endothelium, the effects appear transient as repeated exposure to the IHG stimulus improved resting endothelium-dependent vasodilation.
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PMID:Acute vascular responses to isometric handgrip exercise and effects of training in persons medicated for hypertension. 1664 82

In the present study, we investigated whether measures of brachial artery reactivity were associated with the presence and extent of subclinical coronary atherosclerosis in asymptomatic adults. Electron beam computed tomography was employed to assess the presence and quantity of CAC (coronary artery calcium) in 441 participants (mean age, 61 years; 49% men) without prior history of CHD (coronary heart disease) or stroke, and CAC score was calculated using the method described by Agatston and co-workers [(1990) J. Am. Coll. Cardiol. 15, 827-832] High-resolution ultrasound was employed to measure BAD (brachial artery diameter), FMD (flow-mediated dilatation) and NMD (nitroglycerine-mediated dilatation). CAC score and FMD were log-transformed after adding 1 to reduce skewness. Multivariable logistic and linear regression models based on generalized estimating equations were used to assess whether BAD, FMD and NMD were each independently associated with the presence and quantity of CAC after adjustment for CHD risk factors and use of statin and hypertension medication. CAC was detectable in 64% of participants. After adjustment for age and sex, FMD was not correlated (r=-0.06; P=0.27), BAD was positively correlated (r=0.16; P=0.004) and NMD was inversely correlated in a borderline significant manner (r=-0.10; P=0.084) with log(CAC+1). In multivariable logistic regression analyses, FMD was not associated, whereas higher BAD (P=0.021) and lower NMD (P=0.030) were independently associated with the presence of CAC. In multivariable linear regression analyses, higher BAD (P=0.004) and lower NMD (P=0.016), but not FMD, were independently associated with log(CAC+1). We conclude that greater diameter of the brachial artery and lower vasodilator response to nitroglycerine, but not FMD, are associated with subclinical coronary atherosclerosis.
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PMID:Brachial artery diameter and vasodilator response to nitroglycerine, but not flow-mediated dilatation, are associated with the presence and quantity of coronary artery calcium in asymptomatic adults. 1698 2

Superoxide anion is produced in human platelets predominantly by Nox2-dependent NADPH oxidases. In vitro experiments have shown that it might play a role in modulating platelet functions. The relationship between platelet superoxide production and aggregation remains poorly defined. Accordingly, we aimed to study superoxide production and aggregation in platelets from subjects with significant cardiovascular risk factors (hypertension, hypercholesterolemia, smoking and diabetes mellitus) and from control individuals. Moreover, we studied the effects of novel polyphenol-rich extracts of Aronia melanocarpa (chokeberry) berries on platelet function in vitro. Superoxide production was significantly increased in patients with cardiovascular risk profile when compared to controls, while platelet aggregation in response to either collagen or thrombin were borderline higher, and did not reach statistical significance. Interestingly, no relationship was observed between platelet aggregation ex vivo and platelet superoxide production in either of studied groups. No correlation was found between endothelial function (measured by FMD) and platelet aggregation ex vivo either. Polyphenol-rich extracts of A. melanocarpa berries caused a significant concentration dependent decrease in superoxide production only in patients with cardiovascular risk factors, while no effect was observed in the control group. A. melanocarpa extracts abolished the difference in superoxide production between risk factor patients and controls. A. melanocarpa extracts exerted significant concentration dependent anti-aggregatory effects in both studied groups, which indicated that these effects may be independent of it's ability to modulate superoxide production. The anti-aggregatory effects of chokeberry extracts were similar irrespective of aggregation inducing agent (collagen or thrombin). Moreover, they appear to be independent of platelet NO release as NOS inhibition by L-NAME did not lead to their abrogation.
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PMID:Effects of novel plant antioxidants on platelet superoxide production and aggregation in atherosclerosis. 1722 85

The nitric oxide/cyclic-guanosine 3',5'-monophosphate signaling cascade plays an essential role in cardiovascular homeostasis but its involvement in the pathophysiology of refractory hypertension is unclear. The acute vasodilatory effect of a single oral dose of a phosphodiesterase-5 inhibitor (sildenafil citrate) on the brachial artery dilatation was evaluated in 25 normal healthy volunteers (NL) and in 25 refractory hypertensive patients (RH). Endothelial and vascular smooth muscle functions were assessed two times. First, the brachial artery response to endothelium-dependent (flow-mediated dilatation [FMD]) and independent (glyceryl trinitrate [GTN]) stimuli was examined. The FMD in NL was 14.2+/-3.2% compared to 10.3+/-3.5% in RH (P<0.001) and the GTN-induced responses were 23.5+/-6.3 in NL compared to 18.4+/-5.7% in RH (P<0.001). Two weeks later, the brachial artery responses to FMD were determined before and after the administration of sildenafil citrate. Sildenafil caused a significant, slow and progressive dilatation of the brachial artery until 45 min after administration (4.7+/-3.0%, 6.7+/-3.0% and 9.4+/-3.9% after 15', 30' and 45', respectively, in RH and 3.7+/-1.9%, 7.4+/-2.7% and 10.1+/-3.0%, respectively, in NL). A second FMD stimulus, applied 45 min after ingesting 50mg of sildenafil resulted in an additional significant increase in the vasodilatory response (from 9.4+/-3.9% to 13.0+/-4.0% in RH; P<0.001 and from 10.1+/-3.0 to 14.6+/-4.1 in NL; P<0.001), but this was still significantly less than the response to GTN. Sildenafil citrate caused brachial artery vasodilatation similar to that caused by NO released during FMD in patients with refractory hypertension.
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PMID:Cyclic guanosine monophosphate phosphodiesterase-5 inhibitor promotes an endothelium NO-dependent-like vasodilation in patients with refractory hypertension. 1727 7

Blood pressure variability correlates with circadian rhythmicity in endothelium-derived nitric oxide (NO) production in adults. Young, hypertensive orthotopic heart transplant (OHT) patients have functional abnormalities in NO-dependent signaling pathways that lead to reduced NO bioavailability and endothelial dysfunction. Following acute intravenous infusion of L: -arginine, the amino acid substrate for NO, OHT patients normalize blood pressure (BP) and endothelial function. However, the effects of chronic L: -arginine infusion on circadian BP rhythmicity and endothelial function in OHT patients have not been described. Six OHT patients (9-29 years old), and seven healthy control subjects (19-28 years old) were admitted for 48 hours. Systolic, diastolic, and mean blood pressures (MBP) were recorded hourly. Urine samples were obtained to measure nitrates/nitrites (NO(X)). Brachial artery flow-mediated vasodilatation (FMD; an index of endothelial function) and left ventricular ejection fraction (LVEF) were measured 0, 23, and 48 hours after admission. Intravenous L: -arginine HC1 was infused continuously beginning 24 hours after admission in all subjects. The incidence (50%) and degree (12.0 +/- 9.2%) of nocturnal MBP dipping was significantly less in OHT patients than control subjects. Furthermore, FMD was significantly reduced in OHT patients compared to controls (3.2 +/- 1.1 vs 7.2 +/- 3.1%, p = 0.01). L: -Arginine infusion had no significant effect on 24-hour MBP, LVEF, or nocturnal dipping status in any subject; however, L: -arginine normalized FMD in OHT patients (7.4 +/- 1.8%). Circadian BP variability and endothelial function are impaired in young cardiac transplant patients with medically controlled hypertension, and L: -arginine administration reverses endothelial dysfunction.
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PMID:Endothelial dysfunction and circadian blood pressure rhythmicity in young heart transplant recipients. 1730 45

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