Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

SYMPATHETIC NERVOUS SYSTEM AND HYPERTENSION: Biochemical, electrophysiological, pharmacological and haemodynamic findings support the existence of sympathetic nervous system activation in primary human hypertension. Analysis of regional sympathetic nervous system function, using both neurophysiological methods for measuring sympathetic nerve firing rates, and neurochemical techniques for quantifying regional noradrenaline spillover to plasma has demonstrated activation of the sympathetic nervous outflows to the heart, the kidneys, and skeletal muscle vasculature, particularly in younger patients. The initiating cause of this sympathetic nervous stimulation is unknown, but estimation of central nervous system noradrenaline turnover in hypertensive patients, using measurements of the washout of noradrenaline and its lipophilic metabolites into the internal jugular veins, indicates that activation of forebrain pressor noradrenergic nuclei is the probable underlying mechanism. CONSEQUENCES OF INCREASED SYMPATHETIC ACTIVITY: The sympathetic activation present in human hypertension no doubt contributes to the blood pressure elevation, and is a legitimate target for therapeutic intervention with imidazoline receptor-binding agents such as rilmenidine. In addition, the sympathetic nervous activation seems to have adverse consequences in hypertensive patients beyond initiating the blood pressure elevation. There is evidence that neural vasoconstriction has metabolic effects, in skeletal muscle impairing glucose delivery to muscle, causing insulin resistance and hyperinsulinaemia, and in liver retarding postprandial clearing of lipids, contributing to hyperlipidaemia. Cardiac sympathetic activation is demonstrably a cause of sudden death in heart failure patients; a comparable arrhythmogenic effect is probable in hypertension. A trophic effect of sympathetic activation on cardiovascular growth is also likely, contributing to the development of left ventricular hypertrophy. Rilmenidine, through its central nervous system actions, has been demonstrated to powerfully reduce sympathetic nervous activity in essential hypertension patients. INHIBITING THE SYMPATHETIC SYSTEM: As the clinical consequences of sympathetic nervous activation in essential hypertension appear to go beyond that of hypertension pathogenesis, extending to a causal influence in atherosclerosis development, cardiovascular hypertrophy and cardiac arrhythmias, it is possible that, of all antihypertensive drugs, those inhibiting the sympathetic nervous system might best reduce cardiovascular risk. This remains to be tested.
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PMID:High blood pressure management: potential benefits of I1 agents. 974 6

ALTERATIONS OF THE ENDOTHELIUM: Because of its anatomic position between circulating blood and smooth muscle cells, the vascular endothelium is a prime target for cardiovascular diseases such as hypertension, hypercholesterolemia, diabetes or ischemia. The morphological changes occurring in the endothelium have been known for many years, but it was only recently that the functional alterations have been described. IMPACT OF NO: Under physiological conditions, the vascular endothelium plays a protective role by secreting relaxation factors. In the disease state, the synthesis and release of NO may be reduced or even abolished. The exact significance of endothelium-dependent vasodilatation disorders remains a topic of research, but the properties of NO strongly suggest it is involved in several diseases. For some diseases it is still a question as to whether the observed anomalies are the cause or the consequence of the underlying disease. DISEASE-SPECIFIC CHANGES: NO is known to be reduced in atherosclerosis, either because of less synthesis or accelerated degradation. In different experimental modules of hypertension, the baseline level of NO release appears to be decreased. Conversely, NO release can be normal, reduced or increased in diabetes. In heart failure, there appears to be not only a permanent alteration in NO secretion, but also an increase in factors stimulating vascular contraction, contributing to an altered capacity for vascular adaptation in these patients.
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PMID:[Nitric oxide (NO), vascular protection factor. NO related cardiovascular diseases]. 976 31

PURPOSE OF THE REVIEW. The purpose of this review is to examine the cardiovascular health status of Asian Americans/Pacific Islanders by primary risk factor and review current intervention approaches targeting this population. Asian Americans/Pacific Islanders in the United States have experienced triple digit percentage increases in population for every decade since 1970. Despite their rapidly increasing numbers, little is known about their cardiovascular health status. SEARCH METHODS USED. This article reviews the literature on the demographics, mortality, and prevalence of major cardiovascular risk factors among Asian Americans/Pacific Islanders. Selected intervention programs are also described. SUMMARY OF IMPORTANT FINDINGS. Data on cardiovascular disease mortality for Asian Americans/Pacific Islanders are relatively limited because few states collect ethnically specific mortality statistics. Data on cardiovascular risk factors, particularly smoking and hypertension, for certain Asian American/Pacific Islander groups portend excessive cardiovascular disease burdens. MAJOR CONCLUSIONS. Data specific to ethnic groups comprising Asian Americans and Pacific Islanders need to be called. Also, scientifically valid and linguistically appropriate interventions approved by ethnic community leaders are needed to address Asian Americans/Pacific Islanders.
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PMID:Cardiovascular health among Asian Americans/Pacific Islanders: an examination of health status and intervention approaches. 1014 7

AIM OF THE STUDY: Heart failure is the final clinical presentation of a variety of cardiovascular diseases, such as coronary artery disease, hypertensive, toxic, and inflammatory heart disease. However, the cellular mechanisms responsible for the progressive deterioration of myocardial function observed in heart failure remain unclear and may result from cell death (programmed or not) and from an increase in number of nuclei and in the degree of their ploidy. METHODS: We examined thirty-eight explanted hearts obtained during transplantation for DNA content in the myocytic population. All thirty-eight patients had severe chronic heart failure: 23 had idiopathic dilated cardiomyopathy, and 15 had ischemic cardiomyopathy. Ten hearts of people whose death was not due to primary heart disease or as a consequence of major risk factors of coronary artery disease, including hypertension, diabetes, obesity, or severe atherosclerosis, were used as controls. DNA content in the myocytic population was evaluated using Image Cytometry. RESULTS: The DNA content per nucleus and per myocyte in cardiomyopathic hearts are characterized by: a) a decrease of the diploid DNA content of myocytic nuclei; b) an increase of DNA ploidies higher than 4c; c) a decrease in mononucleated myocytes; d) an increase in binucleated and multinucleated myocytes. The changes are more prominent in dilated cardiomyopathy. e) The total ploidy index, used to calculate the total DNA content, is related to heart weight and ventricular weight. CONCLUSIONS: Ischemic and dilated cardiomyopathies result in reduction of ventricular mass-to-chamber volume ratio and in discrete foci of myocyte cell death, leading to an elevation in systolic and diastolic stress on the remaining viable cells. Therefore mechanical stimuli generated by global and local loading abnormalities associated with end-stage failure may contribute to activate genes implicated in cell proliferation. Observations in this investigation are consistent with recent results documenting that in the presence of overload conditions the myocytes may retain their capacity to proliferate throughout life and this growth reserve mechanism may become operative in response to severe myocardial dysfuntion and overt failure. Polyploidization and multinucleation are prominent phenomena in the end-stage of ischemic and dilated cardiomyopathy in humans.
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PMID:DNA Content in End-Stage Heart Failure. 1035 69

The effects of excess cortisol secretion on blood pressure and fat deposition are well documented, but the importance of this glucocorticoid in controlling these processes in normal individuals is less clear. We studied the relationship between cortisol excretion rate (tetrahydrocortisol [THF]+allo-THF+tetrahydrocortisone [THE]) and a range of important cardiovascular risk factors in 439 normal subjects (238 male) sampled from the North of Glasgow (Scotland) population. There were marked gender differences: female subjects were lighter and had lower blood pressures and cortisol levels, whereas HDL cholesterol was higher. The pattern of cortisol metabolism was also different; the index of 11beta-hydroxysteroid dehydrogenase activity (THF+allo-THF/THE) was lower and that of 5alpha-reductase (allo-THF/THF) was higher. There was a strong correlation of blood pressure (positive), cholesterol (positive), and HDL cholesterol (negative in women, positive in men) with age. Cortisol excretion rate did not correlate with blood pressure but correlated strongly with parameters of body habitus (body mass index and waist and hip measurements [positive]) and HDL cholesterol (negative). With multiple regression analysis, there remained a significant association of cortisol excretion rate with HDL cholesterol in men and women and with body mass index in men. These results suggest that glucocorticoids regulate key components of cardiovascular risk.
Hypertension 1999 Jun
PMID:Cortisol effects on body mass, blood pressure, and cholesterol in the general population. 1037 17

The syndrome of apparent mineralocorticoid excess is a form of hypertension inherited in an autosomal recessive manner. It results from mutations in the gene encoding the kidney isoenzyme of 11 beta-hydroxysteroid dehydrogenase. A number of different mutations have been described. Affected patients present with hypertension, hypokalemia and low levels of plasma renin and aldosterone. The severity of cases vary according to the degree of reduced activity of the enzyme. Treatment with potassium-sparing diuretics is effective. Four young adults with moderate hypertension are presented. They all had hypokalemia, low renin and low aldosterone. The THF + allo-THF/THE ratio was normal or slightly elevated. Treatment with amiloride was effective. They are suspected to be mild cases of the syndrome of apparent mineralocorticoid excess.
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PMID:[Mineralocorticoid-like hypertension. "Apparent mineralocorticoid excess". A hereditary type of hypertension?]. 1057 95

THE RELIEF OF THE RESULTS OF THE HOPE TRIAL WITH RESPECT TO THE INCIDENCE OF CEREBROVASCULAR EVENT UNDER ACE INHIBITOR THERAPY: In 1998, the CAPP trial had raised a serious concern about whether captopril therapy increased the risk of cerebrovascular accidents. When compared with betablocker therapy (+/- diuretics) in 11,000 hypertensives, there was a very worrying number of excess cerebrovascular accidents in the captopril group (+25%) (with no difference in the number of cerebrovascular accidents overall). There were several reasons which led to believe that the captopril was not the causal factor. But a doubt remained. In 1999, the results of the HOPE trial with ramipril, though not primarily for a hypertensive population, provided reassurance beyond the investigators' hopes concerning the value of ACE inhibitors in the prevention of vascular events, including cerebrovascular accidents. THE FRAMINGHAM EXPERIENCE OF LVH AND THE TREATMENT OF HYPERTENSION: The Framingham study reported unique data concerning the effects of antihypertensive therapy on LVH in 10,333 subjects of 45 to 74 years of age followed up for 40 years (1950-1989). As the incidence of antihypertensive therapy increased during the observation period, that of hypertension and LVH decreased in parallel. Although these data were retrospective, they are compatible with a causal relationship between the treatment and regression of LVH. This could explain up to 50% of the decrease in cardiovascular mortality observed in the United States during this period. The Framingham study so reposition, in an epidemiological context, the considerable benefits of antihypertensive therapy and of the regression of the associated LVH. THE SEVERITY OF THE WHO AND IHS RECOMMENDATIONS: Less than 130/85: this is the target value of the blood pressure in adults under antihypertensive therapy according to WHO and IHS. In patients with diabetes or renal failure with proteinuria > 1 g/j, the target is even lower. These recommendations incite physicians to beware of any laxness in the treatment of hypertension. The most recent epidemiological data from France indicates that only a minority of the hypertensive patients under treatment are well controlled and that this advice is probably not superfluous. Moreover, in the decision to treat hypertension (drug therapy or not), these recommendations underline the evaluation of the individual risk of the subject on the basis of associated risk factors, target organ complications and previous history of vascular events.
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PMID:[The best of arterial hypertension in 1999]. 1072 43

The 11 beta-hydroxysteroid dehydrogenase type 2 (11 PHSD2) enzyme inactivates 11 betahydroxy steroids in sodium-transporting epithelia such as the kidney, thus protecting the non-selective mineralocorticoid receptor (MR) from occupation by cortisol in humans. Inhibition by xenobiotics such as liquorice or mutations in the HSD11 B2 gene, as occur in the rare monogenic hypertensive syndrome of apparent mineralocorticoid excess (AME), result in a compromised 11 betaHSD2 enzyme activity, which in turn leads to overstimulation of the MR by cortisol, sodium retention, hypokalaemia, low plasma renin and aldosterone concentrations, and hypertension. Whereas the first patients described with AME had a severe form of hypertension and metabolic derangements, with an increased urinary ratio of cortisol (THF+5alphaTHF) to cortisone (THE) metabolites, more subtle effects of mild 11 beta HSD2 deficiency on blood pressure have recently been observed. Hypertension with no other characteristic signs of AME was found in the heterozygous father of a child with AME, and we described a girl with a homozygous gene mutation resulting in only a slightly reduced 11 beta HSD2 activity causing 'essential' hypertension. Thus, depending on the degree of loss of enzyme activity, 11 beta HSD2 mutations can cause a spectrum of phenotypes ranging from severe, life-threatening hypertension in infancy to a milder form of the disease in adults. Patients with essential hypertension usually do not have overt signs of mineralocorticoid excess, but nevertheless show a positive correlation between blood pressure and serum sodium levels, or a negative correlation with potassium concentrations, suggesting a mineralocorticoid influence. Recent studies revealed a prolonged half-life of cortisol and an increased ratio of urinary cortisol to cortisone metabolites in some patients with essential hypertension. These abnormalities may be genetically determined. A genetic association of a HSD11 B2 flanking microsatellite and hypertension in black patients with end-stage renal disease has been reported. A recent analysis of a CA-repeat allele polymorphism in unselected patients with essential hypertension did not find a correlation between this marker and blood pressure. Since steroid hormones with mineralocorticoid action modulate renal sodium retention, one might hypothesize that genetic impairment of 11 beta HSD2 activity would be more prevalent in salt-sensitive as compared with salt-resistant subjects. Accordingly, we found a significant association between the polymorphic CA-microsatellite marker and salt-sensitivity. Moreover, the mean ratio of urinary cortisol to cortisone metabolites, as a measure for 11betaHSD2 activity, was markedly elevated in salt-sensitive subjects. These findings suggest that variants of the HSD11 B2 gene may contribute to the enhanced blood pressure response to salt in some humans.
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PMID:The role of the 11beta-hydroxysteroid dehydrogenase type 2 in human hypertension. 1093 Jan 96

The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of hypertension. This disorder results from an inability of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-OHSD) to inactivate cortisol to cortisone. The diagnosis of AME is usually based on an elevated ratio of cortisol to cortisone reduced metabolites in the urine [tetrahydrocortisol plus allotetrahydrocortisol to tetrahydrocortisone (THF+alloTHF/THE)]. The principal site of "A" ring reduction is the liver, but AME arises from mutation in the gene encoding 11beta-OHSD2 in the kidney. We used a gas chromatographic/mass spectrometric method to measure the urinary free cortisol (UFF) and free cortisone (UFE) in 24 patients affected by the two variants of AME [19 with the classical form (type I) and 5 with the mild form called AME type II] in order to provide a more reproducible in vivo measure of the renal enzymatic activity. Type I patients were divided into two groups: children under 12 and adults. UFF levels (microg/24 h) did not differ between under-12 controls and AME type I children (mean+/-SD, 9+/-4 and 15+/-12, respectively), but was significantly higher in affected adults compared to controls: (62+/-32 vs 29+/-8, p<0.01). No differences were found between adult controls and AME type II patients (29+/-8 and 37.0+/-14, respectively). UFE was undetectable in 63% of AME type I and significantly lower in AME type II (p<0.05). As a consequence UFF/UFE ratio was significantly higher in AME type I patients both in children and adults compared to controls (AME children: 5.1+/-2.6; normal children: 0.43+/-0.2, p<0.01; AME type I adults: 17.7+/-19.6; normal adults: 0.54+/-0.3 p<0.01). For AME type II, where UFE was detectable in every case, the UFF/UFE ratio was significantly higher than adult controls (2.75+/-1.5 vs 0.54+/-0.3, p<0.01). In conclusion, our study indicates that UFE and UFF/UFE ratio are sensitive markers of 11beta-OHSD2, directly reflecting the activity of the renal isozyme and readily identifying patients with AME. The presence of an altered UFF/UFE ratio in both types of AME, although with different degree of severity, calls for re-evaluation and the classification of AME as a single disorder.
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PMID:Congenital deficiency of 11beta-hydroxysteroid dehydrogenase (apparent mineralocorticoid excess syndrome): diagnostic value of urinary free cortisol and cortisone. 1122 27

PURPOSE OF THE STUDY: The purpose of this study is to describe the prevalence of coronary artery disease &lpar;CAD&rpar; and provide a review of the risk factors associated with CAD in Asian Indians. SEARCH METHODS USED: The authors extensively reviewed numerous British and international studies and the more limited number of studies in India and the US. SUMMARY OF IMPORTANT FINDINGS: Asian Indians have one of the highest rates of CAD. Conventional risk factors such as high blood pressure, high serum total cholesterol level, cigarette smoking, high fat diet, and obesity consistently fail to fully explain these high rates. There appears to be a strong role of insulin resistance and abdominal obesity, both of which have a high prevalence in Asian Indians. Various dyslipidemic disorders in Asian Indians such as low levels of HDL cholesterol, elevation of triglyceride, elevation of LDL cholesterol and elevation of lipoprotein &lpar;a&rpar; may also have a role. CONCLUSIONS: We hypothesize that against a background of higher susceptibility to CAD among Asian Indians, as characterized by insulin resistance, abdominal obesity and dyslipidemic disorders, conventional risk factors for CAD are also important. A genetic predisposition to CAD is suggested by high levels of lipoprotein &lpar;a&rpar; in Asian Indians. This would suggest that more aggressive identification and modulation of all known risk factors are necessary among Asian Indians along with a compelling need for further epidemiological studies in this population. RELEVANCE TO ASIAN PACIFIC ISLANDER AMERICAN POPULATIONS: The marked differences in the rates of CAD among Asian Indians, compared with Chinese, Japanese, Filipino, other Asians and Whites are discussed. KEY WORDS: Asian Indians, coronary artery disease, epidemiology, disease prevalence, risk factors, insulin resistance, dyslipidemic disorders, triglycedide, high density lipoprotein; lipoprotein &lpar;a&rpar;
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PMID:Coronary Artery Disease in Asian Indians: Prevalence and Risk Factors. 1156 49


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