Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An impaired synthesis of nitric oxide (NO) by the vascular endothelium has been implicated in the pathogenesis of essential hypertension (EH). The possible association between a variable number of tandem repeats (VNTR) polymorphism in intron 4 of the endothelial constitutive NO synthase (ecNOS) gene and EH in Japanese subjects was investigated. A total of 123 individuals with EH and 120 normotensive control subjects were studied. The VNTR region of the ecNOS gene was amplified by the polymerase chain reaction to determine the number of repeats, and the allele frequencies were compared between the hypertensive and normotensive groups. Two alleles, containing four and five repeats, were identified. The overall distributions of allele frequencies differed significantly between the two groups, with the four-repeat allele more frequent in the EH group than in the normotensive group (P = .00027, odds ratio = 4.0). The four-repeat allele of the ecNOS gene was thus associated with EH and may be a genetic marker of this disease in Japanese subjects.
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PMID:Association of a variable number of tandem repeats in the endothelial constitutive nitric oxide synthase gene with essential hypertension in Japanese. 950 61

The contributing role of vascular endothelium in the development of hypertension-related vascular damage is well accepted. Salt-sensitive hypertension is characterized by a cluster of renal, hormonal, and metabolic derangements that might favor the development of cardiovascular and renal damage. To evaluate endothelial involvement in salt-sensitive essential hypertension, plasma levels of several markers of endothelial damage such as endothelin-1 (ET-1), von Willebrand factor (vWf), and soluble (S-) adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and 24-hour urinary albumin excretion (UAE) were measured in 39 nondiabetic, nonobese, never-treated essential hypertensive patients after intermediate (120 mmol/d), high (220 mmol/d), and low (20 mmol/d) NaCl diets. Patients were classified as salt sensitive (n=18) or salt resistant (n=21) according to their blood pressure responses to changes in dietary NaCl intake. Salt-sensitive hypertensives showed higher plasma ET-1 (P<0.05), vWf (P<0.005), and S-E-selectin levels (P<0.04) and increased UAE (P<0.05) than salt-resistant hypertensives. By contrast, circulating S-ICAM-1 and S-VCAM-1 concentrations were not significantly higher in salt-sensitive (596. 56+/-177.05 ng/mL and 541.06+/-157.84 ng/mL, respectively) than salt-resistant patients (516.86+/-147.99 ng/mL and 449.48+/-158.91 ng/mL, respectively). During the intermediate NaCl diet, plasma ET-1 responses to oral glucose load were greater in salt-sensitive (P<0. 05) than in salt-resistant patients. A marked (P<0.05) hyperinsulinemic response to oral glucose load was evident in salt-sensitive but not salt-resistant patients after each diet. This study shows increased plasma levels of the endothelium-derived substances E-selectin, vWf, and ET-1 in salt-sensitive hypertensives. Our findings support the hypothesis that salt sensitivity is correlated with an increased risk for developing hypertension-related cardiovascular damage.
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PMID:Clustering of endothelial markers of vascular damage in human salt-sensitive hypertension: influence of dietary sodium load and depletion. 982 45

A change in endothelial function is a common phenomenon in patients with essential hypertension and in animals with hypertension, whether primary or induced by a salt-rich diet. In hypertensive subjects, there may be a change in the synthesis, or the effect, of nitric oxide. Nevertheless, hypertensive vasoconstriction is at present associated, above all, with the degradation of this mediator by free radicals, such as the superoxide anion, released in the dysfunctional vascular endothelium. These radicals are also formed when hypoxanthine is turned into xanthine, and when the latter becomes uric acid, both having been catalysed by the enzyme xanthine oxidase. In physiological conditions, the concentration of superoxide radicals remains low within the organism as a result of its reaction with the superoxide dismutase enzyme. However, in pathological situations, such as arterial hypertension, there may be an increase in the production of these radicals or a deficiency of the superoxide dismutase enzyme. In hypertensive patients, the release of vasoconstrictor peroxides derived from the activity of cyclo-oxygenase in the endothelium and the vascular smooth muscle is also important. The excess free radicals released by the dysfunctional endothelium also stimulate the synthesis of these contracting agents. Moreover, it should not be forgotten that endothelin-1, which is similarly synthesized and released in the vascular endothelium, is the most powerful known endogenous vasoconstrictor. This peptide would therefore play a prominent part in some forms of hypertension. Although no changes in endothelin plasma levels have been found in essential hypertension, there may be an increase in its local concentration. It should be borne in mind that endothelin could strengthen the effect of other vasoconstrictors. Moreover, it may also provoke the release of free radicals and of cyclo-oxygenase-derived vasoconstrictor factors. The latest theories therefore indicate that the increase in vasoconstriction, which characterizes arterial hypertension, is associated with a greater production of free radicals. At the present time, antioxidant agents and xanthine oxydase-inhibiting compounds are being used to treat hypertension and other pathologies linked to endothelial dysfunction. In addition, it is thought that the therapeutic benefit of some anti-hypertensive drugs, such as calcium antagonists and angiotensin-converting enzyme inhibitors, could be in part due to the inhibition of the production of free radicals that they provoke.
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PMID:Endothelial dysfunction and hypertensive vasoconstriction. 1043 69

Ninty patients with mild to moderate essential hypertension (EH) were randomly divided into three groups and treated with Enalapril (E), Metoprolol (M) and Nifedipine (N) respectively. After a six-week-treatment, SBP and DBP of each of the three groups decreased significantly (vs. pre-treatment, P < 0.001). Plasma concentration of ET, NO, cGAMP and MDA in group M remained unchanged, and that of MDA in group N, especially of the stage II EH, decreased remarkably (vs. pretreatment, P < 0.05; vs. that of stage I EH, P < 0.05). While that of ET, NO, cGMP, and MDA in group E changed significantly (vs. Pretreatment, P < 0.01) and that of ET and MDA of stage II EH in group E exhibited more remarkable changes (vs. that of stage I, P < 0.05). It is suggested that E, and at some degree N, may protect the vascular endothelium from being damaged in EH, and also may contribute to prevent EH from development.
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PMID:[Effect of antihypertensive agents on plasma endothelin, nitric oxide and so on in essential hypertension]. 1043 66

1. Experimental hypertension is associated with several functional alterations of vascular endothelium and smooth muscle, but relatively few studies have examined the control of arterial tone in isolated vascular preparations from patients with essential hypertension. Therefore, we compared functional characteristics in vitro of distal ring segments of the mesenteric artery from 17 hypertensive and 22 normotensive humans. 2. Arterial constrictor responses induced by cumulative addition of Ca(2+) in the presence of noradrenaline (NA) were more effectively inhibited by the Ca(2+) entry blocker nifedipine (0.5 nM) in hypertensive than normotensive subjects (by 55.4+/-4.9, n=17 and 35.0+/(-5.2%), n=22, respectively). Also the contractions elicited by high concentrations of KCl were more effectively inhibited by nifedipine in arterial rings from hypertensive than normotensive patients (by 38.9+/(-3.7), n=17 and 20. 2+/(-4.6%), n=22, respectively). However, the concentration-response curves of contractions to NA, serotonin and KCl in the absence of nifedipine were similar between the study groups. 3. The concentration-response curves of endothelium-dependent relaxations to acetylcholine and Ca(2+) ionophore A23187, as well as of endothelium-independent relaxations to the nitric oxide donor nitroprusside, beta-adrenoceptor agonist isoprenaline and K+ channel opener cromakalim did not show any differences between the groups. Moreover, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (0.1 mM) almost abolished the relaxations to acetylcholine and Ca(2+) ionophore in both groups, indicating that these responses were largely mediated by nitric oxide. The function of arterial sodium pump was evaluated by relaxations elicited by the return of K+ upon contractions induced by K+-free solution. The rate of K+-relaxation was similar in hypertensive and normotensive arteries (for all these responses n=20 - 22 in the normotensive and 15 - 17 in the hypertensive group). 4. These results suggest abnormal function of voltage-dependent Ca(2+) channels in arterial smooth muscle of hypertensive patients, whereas vascular responses to endothelium-dependent and -independent vasodilators and classical contractile agents were similar between hypertensive and normotensive subjects. The present findings support the view that blockade of voltage-dependent Ca(2+) channels is an effective means of reducing arterial tone in essential hypertension.
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PMID:Control of vascular tone in isolated mesenteric arterial segments from hypertensive patients. 1045 33

Morphofunctional aspects of the immune system (spleen, Peyer's patches, peripheral blood) were studied in patients with essential hypertension, rheumatic lesions of the heart and rheumatic patients after surgery. Surgical intervention caused considerable immunodepression. The entire system of coordinated functioning of immune organs got impaired. Immunodepressive restructuring of lymphoid organs affects all the structural units. Changes of the vascular-stromal complex are accompanied by changes in the most sensitive and complex mechanisms of the immune system such as vascular endothelium and population of progenitor cells. Metabolic basis transport and synthesis in the endothelium are perversed. In the progenitor cells proliferative activity of lymphocytes was sharply decreased while there was an increase in the function of suppressor T-lymphocytes. It is concluded that desynchronization of enzyme functioning in the vascular component of both the spleen and lymphoid system of the intestine can be regarded as a sign of disintegration of the entire system of immune organs during stress caused by a surgical intervention.
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PMID:[Morphofunctional characteristics of human immune system in surgical stress]. 1066 13

Previous studies have demonstrated that elevated plasma leptin concentrations are associated with essential hypertension. It has also recently been shown that leptin plays a promoting role in angiogenesis, and the vascular endothelium expresses the long form of leptin receptor. Those data led us to hypothesize that leptin might contribute to end-organ damage in hypertension. Thus, in the present study we evaluated the relationship between plasma leptin concentrations and hypertensive retinopathy (HR). One hundred and eleven patients newly diagnosed with essential hypertension [EHT; mean age, 43.5 +/-10.7 yr; body mass index (BMI), 28.1 +/- 4.4 kg/m2; male/female ratio, 71/40] and 79 healthy normotensive control subjects (NT; mean age, 43.6 +/- 9.2 yr; BMI, 28.2 +/- 3.3 kg/m2; male/female ratio, 50/29) were enrolled in the study. For the assessment of retinopathy according to the Keith-Wagener classification, direct and indirect ophthalmoscopy were performed in all subjects after dilatation of the pupils. Plasma leptin levels were significantly higher in EHT (11.8 +/- 11.1 ng/mL) than in NT (7.2 +/- 5.1 ng/mL) (P = 0.003). Plasma leptin concentrations were strongly correlated with BMI in both EHT (r = 0.45; P = 0.001) and NT (r = 0.38; P = 0.001) groups. Plasma leptin in patients with grade 2 HR (24.8 +/- 15.8 ng/mL; n = 22) was significantly higher than that in patients with grade 1 HR (16.1 +/- 4.9 ng/mL; n = 29; P = 0.001), grade 0 HR (5.1 +/- 3.1 ng/mL; n = 60; P = 0.001), and NT (P = 0.001). Plasma leptin in patients with grade 1 HR was also significantly higher than that in patients without retinopathy (P = 0.001) or in NT (P = 0.001). The estimated threshold of plasma leptin concentration for HR was 10.2 ng/mL. This critical leptin level served largely to separate patients with retinopathy from those without retinopathy. In summary, our results show that plasma leptin concentrations increase progressively with higher grades of hypertensive retinopathy even after correction for BMI, suggesting that a critical leptin level is needed for the development of retinopathy. Elevated concentrations of plasma leptin might be secondary to release of leptin by the vascular endothelium damaged by high blood pressure, as an epiphenomenon. However, a pathogenic role for leptin in hypertensive retinopathy cannot be excluded.
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PMID:Is leptin associated with hypertensive retinopathy? 1069 Aug 76

Background: Thrombomodulin (TM) is a membrane glycoprotein in the vascular endothelium. It may be cleaved from endothelial cells and released into the circulation. The plasma TM level depends on the integrity of the endothelium and the clearance of the molecule. The physiological role of soluble TM forms is still unclear. The clinical significance of elevated levels of TM in various pathologic conditions is not well established yet. To analyze variations of plasma TM level in different clinical situations, its concentrations in patients with three groups of diseases were measured and compared with those in healthy subjects. Methods: Plasma samples from 23 patients at risk for development of vascular complications [essential hypertension (EH), stages 1 and 2], 31 patients with inflammatory bowel diseases [Crohn's disease (IBD), mostly in the active stage], and 19 patients with malignant tumors [gastric carcinoma (NEO)], were analyzed for soluble TM with an enzyme immunoassay kit. Results: In the group of patients with the early stages of EH and with non-active IBD, no significant changes were found in comparison to the healthy subjects. In the patients with active IBD and mainly with NEO, soluble TM was significantly increased (P<0.05 and P<0.001, respectively). Conclusions: Our TM levels failed to demonstrate increased endothelial damage in the early stage of EH. This suggests that TM is released into the plasma only by true endothelial cell damage during the development of vascular complications. Probably a certain degree of endothelial injury is necessary for an increase in plasma. In the active stage of IBD and in NEO, soluble TM appears to be derived not only from injured endothelial cells, but may also be proteolytically cleaved from membrane TM by proteases. There may also be increased synthesis of TM in activated and/or transformed cells.
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PMID:Thrombomodulin as a marker of endothelium damage in some clinical conditions. 1074 50

We recently discovered that patients with essential hypertension have a markedly impaired capacity for stimulated release of tissue plasminogen activator (tPA) from vascular endothelium. This defect may reduce the chance of timely spontaneous thrombolysis in case of an atherothrombotic event. We now investigated whether increased intraluminal pressure as such may depress vascular tPA release or downregulate its gene expression. Segments of human umbilical veins were studied in a new computerized vascular perfusion model under steady laminar flow conditions for 3 or 6 hours. Paired segments were perfused at high or physiological intraluminal pressure (40 versus 20 mm Hg) under identical shear stress (10 dyne/cm(2)). Quantitative immunohistochemical evaluation of cellular tPA immunoreactivity was performed on paraffin-embedded 5-microm vascular sections. tPA mRNA in endothelial cells was quantified with reverse transcription real-time TaqMan polymerase chain reaction with GAPDH as endogenous control. Secretion of tPA into perfusion medium was evaluated with SDS-PAGE and Western blotting, followed by densitometric quantification. High-pressure perfusion downregulated tPA gene expression with a 38% decrease in tPA mRNA levels (P=0.01) compared with vessels perfused under normal intraluminal pressure. tPA release into the perfusion medium was markedly suppressed by high pressure (P<0.01 ANOVA). The intracellular storage pool of tPA was reduced after 6 but not 3 hours. Thus, elevated intraluminal pressure downregulates tPA gene and protein expression and inhibits its release from the endothelium independently of shear stress. The defective capacity for stimulated tPA release that we demonstrated in patients with essential hypertension might thus be an effect of the elevated intraluminal pressure per se.
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PMID:Elevated intraluminal pressure inhibits vascular tissue plasminogen activator secretion and downregulates its gene expression. 1077 76

The impact of hypertension on microvascular permeability and nitric oxide-mediated endothelial vasomotion in humans has been studied by measuring either the transcapillary albumin escape rate (TERalb, a measure of permeability through systemic capillary endothelium where most of the albumin permeation takes place) and forearm vasodilatation to locally infused acetylcholine (used as a probe for the nitric oxide-releasing potential of arteriolar endothelial cells). It is unknown, however, how the two parameters relate to each other in the same hypertensive subject. This piece of evidence may enhance our understanding about the relative effect of hypertension on two biological functions (ie, permeability and nitric oxide-mediated vasomotion), both dependent on vascular endothelium, and also may allow to appreciate in greater detail the profile of parameters frequently used as markers of microvascular dysfunction in human hypertension. For these reasons, TERa1b (the 1-h decline rate of intravenous 125I-albumin) and forearm vasodilatation (strain gauge venous plethysmography) to graded intraarterial acetylcholine infusion were measured in 44 never-treated men with uncomplicated essential hypertension, and 15 male normotensive controls with comparable age, lipids, and proportion of current smokers. TERalb was increased in patients, whereas acetylcholine-mediated vasodilatation did not differ significantly between the two groups, indicating a heterogeneous impact of elevated blood pressure on capillary permeability and endothelial vasomotion in still uncomplicated mild to moderate essential hypertensive patients. The dissociation between TERalb and forearm responsiveness to acetylcholine also demonstrates that different endothelial-dependent biologic parameters do not behave uniformly in human hypertension.
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PMID:Transvascular albumin leakage and forearm vasodilatation to acetylcholine in essential hypertension. 1077 29


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