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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper discusses the role of endothelial dysfunction in human hypertension, especially in relation to small resistance artery structure, as well as the effects of anti-hypertensive drugs on endothelial function of small arteries in human and experimental hypertension. A significant impairment of endothelial function was observed in human essential hypertension as well as in secondary forms of hypertension. No correlation was observed with vascular structure. In animal models of genetic hypertension there is substantial evidence for a beneficial effect of anti-hypertensive treatment with angiotensin converting enzyme (ACE) inhibitors, calcium entry blockers and angiotensin II receptor blockers on endothelial function in small resistance arteries. A significant improvement in endothelial dysfunction may be observed in hypertensive patients after prolonged treatment with ACE inhibitors (cilazapril, lisinopril), calcium entry blockers (nifedipine), and angiotensin II receptor blockers (losartan), while atenolol and hydrochlorotiazide proved to be ineffective in this regard despite similar blood pressure reductions. We conclude that: (i) the development of hypertension is usually associated with the presence of endothelial dysfunction in small resistance arteries of essential hypertensive patients; (ii) vascular structure does not seem to be the major determinant of endothelial function, at least in subcutaneous small resistance arteries; (iii) anti-hypertensive therapy with ACE inhibitors, angiotensin II receptor blockers and calcium entry blockers may improve endothelial function; (iv) a decrease in blood pressure seems to be necessary but not sufficient to obtain a beneficial effect on the endothelium in humans.
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PMID:Endothelial factors and microvascular hypertensive disease. 1181 69

Essential hypertension has a heritability as high as 30-50%, but its genetic cause(s) has not been determined despite intensive investigation. The renal dopaminergic system exerts a pivotal role in maintaining fluid and electrolyte balance and participates in the pathogenesis of genetic hypertension. In genetic hypertension, the ability of dopamine and D(1)-like agonists to increase urinary sodium excretion is impaired. A defective coupling between the D(1) dopamine receptor and the G protein/effector enzyme complex in the proximal tubule of the kidney is the cause of the impaired renal dopaminergic action in genetic rodent and human essential hypertension. We now report that, in human essential hypertension, single nucleotide polymorphisms of a G protein-coupled receptor kinase, GRK4gamma, increase G protein-coupled receptor kinase (GRK) activity and cause the serine phosphorylation and uncoupling of the D(1) receptor from its G protein/effector enzyme complex in the renal proximal tubule and in transfected Chinese hamster ovary cells. Moreover, expressing GRK4gammaA142V but not the wild-type gene in transgenic mice produces hypertension and impairs the diuretic and natriuretic but not the hypotensive effects of D(1)-like agonist stimulation. These findings provide a mechanism for the D(1) receptor coupling defect in the kidney and may explain the inability of the kidney to properly excrete sodium in genetic hypertension.
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PMID:G protein-coupled receptor kinase 4 gene variants in human essential hypertension. 1190 38

Currently, one of the methods of comprehensive evaluation of patient health status is quality of life assessment. In the management of hypertension, evaluation of quality of life helps in individualization of therapy and improves its efficiency. The aim of the study was to compare the general quality of life between patients with essential hypertension and normal blood pressure values, and to analyse the effect of socio-demographic factors on the quality of life. An open questionnaire was distributed among 1539 patients (775 men and 764 women), aged from 18 to 88 years (x = 51.7 +/- 14.6 years) with essential hypertension detected at least 3 months earlier, referring to treatment for the first time or already treated by general practitioners and the Outpatient Department on Hypertension of the I Cardiac Department. Hypotensive treatment was given to 82.6% of the subjects, whereas 17.4% were untreated. A group of 995 subjects (459 men and 536 women) aged from 18 to 82 years (x = 48.6 +/- 11.2 years) with normal blood pressure values served as controls. All subjects provided data on education employment, body mass index, duration of arterial hypertension, family history, target organ damage, co-morbidity, blood pressure value, heart rate and pharmacological treatment. All subjects filled out a standardised questionnaire--Psychological General Well-Being (PGWB), which evaluated the general quality of life and its sin dimensions: Anxiety, Depressive mood, Subjective Well-being, Self-control, General health and Vitality. Statistical analysis included descriptive statistics, analysis of variance and multiple regression. The general quality of life in patients with essential hypertension was significantly lower than that in age-matched normotensives. The quality of life in women was lower than that in men irrespective of arterial hypertension presence. The quality of life was decreasing with age both in hypertensive and normotensives; however in hypertensive men there was a trend towards improved quality of life above 65 years of age in contrast to age-matched women in whom the quality of life deteriorated. The quality of life in untreated hypertensives was lower than that in age-matched healthy subjects, but until 40 years of age was higher than in treated age-matched hypertensives. The quality of life was related to the level of education, employment and familial history of hypertension. A lower quality of life was observed among hypertensives with coronary heart disease and diabetes. Multiple regression analysis revealed that gender, education, age and familial hypertension were the socio-demographic factors, which independently affected the quality of life among hypertensives. These factors accounted for 32.7% of the observed variance of quality of life. In normotensives subjects the independent factors were gender, age, education and employment--accounting for 65.8% of variance of quality of life.
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PMID:[Quality of life in patients with essential arterial hypertension. Part I: The effect o socio-demographic factors ]. 1293 55

Dopamine is an important regulator of blood pressure. Its actions on renal hemodynamics, epithelial transport and humoral agents such as aldosterone, catecholamines, endothelin, prolactin, pro-opiomelanocortin, renin and vasopressin place it in central homeostatic position for regulation of extracellular fluid volume and blood pressure. Dopamine also modulates fluid and sodium intake via actions in the central nervous system and gastrointestinal tract, and by regulation of cardiovascular centers that control the functions of the heart, arteries and veins. Abnormalities in dopamine production and receptor function accompany a high percentage of human essential hypertension and several forms of rodent genetic hypertension. Some dopamine receptor genes and their regulators are in loci linked to hypertension in humans and in rodents. Furthermore, single nucleotide polymorphisms (SNPs) of genes that regulate dopamine receptors, alone or via the interaction with SNPs of genes that regulate the renin-angiotensin system, are associated with human essential hypertension. Each of the five dopamine receptor subtypes (D1, D2, D3, D4 and D5) participates in the regulation of blood pressure by mechanisms specific for the subtype. Some receptors (D2 and D5) influence the central and/or peripheral nervous system; others influence epithelial transport and regulate the secretion and receptors of several humoral agents (e.g., the D1, D3 and D4 receptors interact with the renin-angiotensin system). Modifications of the usual actions of the receptor can produce blood pressure changes. In addition, abnormal functioning of these dopamine receptor subtypes impairs their antioxidant function.
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PMID:Regulation of blood pressure by dopamine receptors. 1461 Mar 23

The locus ceruleus (LC) contains a high density of angiotensin II (AII) receptors. The role of AII receptors at the LC in genetic hypertension and organ function is unclear. Spontaneously hypertensive (SHR) rats and Wistar-Kyoto (WKY) rats were studied, and blood pressure of animals was measured using the tail-cuff method. Animals were decapitated and the heart weight (HW) and testicular weight (TW) of animals measured. AII receptor binding was carried out by incubating the LC tissue sections with 200 pM [(125)I]-AII receptor ligand, and measured using quantitative autoradiography. Results showed that the HW/BW ratio was significantly higher in SHR rats than WKY rats. However, the TW/BW ratio was higher in SHR rats than WKY rats only at two hypertensive stages, whereas AII receptor binding capacity in the LC was also statistically higher in SHR rats than WKY rats. Results indicated that cardiac and testicular hypertrophies were related to higher AII receptor binding in the LC of SHR rats, when compared with WKY rats. Interestingly, the literature shows that there is an LC-testes axis. In conclusion, this study indicated that AII receptors in the LC are associated with genetic hypertension, and testicular weight could be a reasonable index for essential hypertension.
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PMID:Angiotensin II receptor binding in the locus ceruleus of spontaneously hypertensive rats and Wistar-Kyoto rats: a quantitative autoradiographic study with references to hypertension and cardiac/testicular hypertrophy. 1506 16

The deletion of thiazide-sensitive Na-Cl cotransporter ( TSC, SLC12A3) causes Gitelman's syndrome characterized by low blood pressure, while deletions of the WNK1 ( PRKWNK1) and WNK4 ( PRKWNK4) genes cause familial hypertension known as pseudohypoaldosteronism type II. Recent studies have revealed that cell surface expression of TSC is regulated by WNK1 and WNK4. We hypothesized that molecular variations in TSC, WNK1, and WNK4 could lead to an increased morbidity of hypertension. We identified 52, 35, and 21 polymorphisms in Japanese hypertensives by sequencing the entire coding regions of TSC, WNK1 and WNK4, respectively. Twenty-one representative polymorphisms were genotyped in 1,818 Japanese individuals (771 subjects with hypertension and 1,047 controls) randomly sampled in Suita city. The results indicated that the systolic blood pressure in men with the CT+TT genotype in WNK4 C14717T was 3.1 mmHg higher than those with the CC genotype ( p=0.042) after adjustment with confounding factors such as age, BMI, hyperlipidemia, diabetes mellitus, antihypertensive drug use, smoking, and drinking. Multivariate logistic regression analysis (with adjustment for the same parameters) in men revealed that the odds ratio for the presence of hypertension of the CT+TT genotype in C14717T to the CC genotype was 1.62 ( p=0.010, 95% confidence interval, 1.12-2.33). Association of TSC and WNK1 with hypertension was not observed. In conclusion, our study suggests the possible involvement of WNK4 in essential hypertension in a Japanese general population.
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PMID:Identification of 108 SNPs in TSC, WNK1, and WNK4 and their association with hypertension in a Japanese general population. 1530 83

Abnormalities in dopamine production and receptor function have been described in human essential hypertension and rodent models of genetic hypertension. All of the five dopamine receptor genes (D1, D2, D3, D4, and D5) expressed in mammals and some of their regulators are in loci linked to hypertension in humans and in rodents. Under normal conditions, D1-like receptors (D1 and D5) inhibit sodium transport in the kidney and the intestine. However, in the Dahl salt-sensitive and spontaneously hypertensive rats, and humans with essential hypertension, the D1-like receptor-mediated inhibition of sodium transport is impaired because of an uncoupling of the D1-like receptor from its G protein/effector complex. The uncoupling is genetic, and receptor-, organ-, and nephron segment-specific. In human essential hypertension, the uncoupling of the D1 receptor from its G protein/effector complex is caused by an agonist-independent serine phosphorylation/desensitization by constitutively active variants of the G protein-coupled receptor kinase type 4. The D5 receptor is also important in blood pressure regulation. Disruption of the D5 or the D1 receptor gene in mice increases blood pressure. However, unlike the D1 receptor, the hypertension in D5 receptor null mice is caused by increased activity of the sympathetic nervous system, apparently due to activation of oxytocin, V1 vasopressin, and non-N-methyl D-aspartate receptors in the central nervous system. The cause of the activation of these receptors remains to be determined.
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PMID:D5 dopamine receptor knockout mice and hypertension. 1552 60

Abnormalities in dopamine production and receptor function have been described in human essential hypertension and rodent models of genetic hypertension. Under normal conditions, D(1)-like receptors (D(1) and D(5)) inhibit sodium transport in the kidney and intestine. However, in the Dahl salt-sensitive and spontaneously hypertensive rats (SHRs) and in humans with essential hypertension, the D(1)-like receptor-mediated inhibition of epithelial sodium transport is impaired because of an uncoupling of the D(1)-like receptor from its G protein/effector complex. The uncoupling is receptor specific, organ selective, nephron-segment specific, precedes the onset of hypertension, and cosegregates with the hypertensive phenotype. The defective transduction of the renal dopaminergic signal is caused by activating variants of G protein-coupled receptor kinase type 4 (GRK4: R65L, A142V, A486V). The GRK4 locus is linked to and GRK4 gene variants are associated with human essential hypertension, especially in salt-sensitive hypertensive subjects. Indeed, the presence of three or more GRK4 variants impairs the natriuretic response to dopaminergic stimulation in humans. In genetically hypertensive rats, renal inhibition of GRK4 expression ameliorates the hypertension. In mice, overexpression of GRK4 variants causes hypertension either with or without salt sensitivity according to the variant. GRK4 gene variants, by preventing the natriuretic function of the dopaminergic system and by allowing the antinatriuretic factors (e.g., angiotensin II type 1 receptor) to predominate, may be responsible for salt sensitivity. Subclasses of hypertension may occur because of additional perturbations caused by variants of other genes, the quantitative interaction of which may vary depending upon the genetic background.
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PMID:Functional genomics of the dopaminergic system in hypertension. 1554 30

During the past decade, it has become evident that dopamine acts not only as a classical neurotransmitter in the central and peripheral nervous system but also as an autocrine, paracrine and/or endocrine substance in peripheral, non-neuronal tissues. This work is aimed to review some of the recent aspects related to the physiological features and effects of renal origin dopamine. Renal dopamine is synthesized in the proximal tubule epithelial cells. Newly formed dopamine leaves the cellular compartment by crossing the apical cell border and the basolateral membrane side. Dopamine exerts its intrarenal action via specific cell surface receptors, differentially expressed along the nephron and other structural components of renal tissue. These receptors have been classified into five types. D1 and D5 receptors are linked to stimulation, while D2, D3 and D4 receptors are linked to inhibition of adenylyl cyclase. Renal dopamine affects electrolyte and fluid balance by regulation of renal excretion of electrolytes and water through actions on renal hemodynamics and tubular, epithelial transport. The importance of intrarenally produced dopamine as a natriuretic hormone is reflected by its capacity to inhibit the majority of sodium transporters (Na+K+ATPase, Na+/H+-exchanger) in the entire nephron. Numerous clinical and animal, experimental observations suggest that dopamine coordinates the effects of antinatriuretic and natriuretic factors and indicate that the intact renal dopamine system is of major importance for maintenence of sodium homeostasis and systemic blood pressure. Sodium retention leads to an increase in renal dopamine tonus. This function is, due to deficient renal dopamine production and/or a D1 receptor G-protein coupling defect, lost in human essential hypertension and in some animal models of genetic hypertension. A better knowledge of molecular bases of these changes may contribute to the development of specific diagnostic and therapeutic approaches in essential as well as secondary forms of hypertension.
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PMID:[Recent findings regarding physiological characteristics and effects of renal dopamine]. 1562 84

Genetic studies in humans and rodent models should help to identify altered genes important in the development of cardiovascular diseases, such as hypertension. Despite the considerable research effort, it is still difficult to identify all of the genes involved in altered blood pressure regulation thereby leading to essential hypertension. We should keep in mind that genetic hypertension and other cardiovascular diseases might develop as a consequence of early errors in well-co-ordinated systems regulating cardiovascular homoeostasis. If these early abnormalities in the ontogenetic cascade of expression of genetic information occur in critical periods of development (developmental windows), they can adversely modify subsequent development of the cardiovascular system. The consideration that hypertension and/or other cardiovascular diseases are late consequences of abnormal ontogeny of the cardiovascular system could explain why so many complex interactions among genes and environmental factors play such a significant role in the pathogenesis of these diseases. The detailed description and precise time resolution of major developmental events occurring during particular stages of ontogeny in healthy individuals (including advanced knowledge of gene expression) could facilitate the detection of abnormalities crucial for the development of cardiovascular alterations characteristic of the respective diseases. Transient gene switch-on or switch-off in specific developmental windows might be a useful approach for in vivo modelling of pathological processes. This should help to elucidate the mechanisms underlying cardiovascular diseases (including hypertension) and to develop strategies to prevent the development of such diseases.
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PMID:Developmental windows and environment as important factors in the expression of genetic information: a cardiovascular physiologist's view. 1703 66


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