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

Epidemiologic studies have shown that insulin is a risk factor for coronary heart disease (CHD). Clinical studies have also demonstrated positive correlations between insulin and blood pressure, triglycerides, total cholesterol, fibrinogen, and plasminogen activator inhibitor. Moreover, there is an inverse correlation between insulin and high-density lipoprotein (HDL). These studies have provided evidence in support of the biologic plausibility of epidemiologic observations, but they have not clearly established insulin's role in the pathogenesis of human cardiovascular diseases (CVD) such as hypertension. In fact, there is considerable evidence that insulin resistance (abnormal nonoxidative glucose disposal), not hyperinsulinemia, is the primary insulin-related abnormality in human hypertension, and that hyperinsulinemia occurs as a response to insulin resistance. Skeletal muscle appears to be the primary site of insulin resistance in essential hypertension, although other organs, such as the kidneys and liver--key sites for cell and water homeostasis and lipoprotein regulation, respectively--may respond normally to insulin. Adipocytes also appear to be a site of insulin resistance. Thus, the putative interrelationship between hyperinsulinemia and insulin resistance, on the one hand, and with blood pressure and lipoproteins, on the other, is a complex one and may involve organ-specific insulin resistance. Altered cation transport is one of several mechanisms by which insulin resistance might raise blood pressure. The Na+, K(+)-ATPase and Ca(2+)-ATPase pumps are insulin sensitive. Thus, when insulin resistance is present, the activity of these pumps in the smooth muscle of the arterial wall might be reduced. This would lead to an intracellular accumulation of sodium and calcium, thereby sensitizing the vascular wall to pressor substances. Moreover, secondary hyperinsulinemia will occur, and insulin has been shown to stimulate sympathetic nervous system activity and to increase renal tubular absorption of sodium. Insulin is also a growth factor and therefore might have a trophic effect on the vessel wall, one that could initiate and/or sustain hypertension as well as atherosclerosis. Abnormal lipoprotein metabolism is yet another possible explanation for the accelerated atherosclerosis that has been observed in persons with abnormal carbohydrate tolerance and insulin resistance. Hyperinsulinemia and insulin resistance both play a role in the expression of elevated very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels as well as in the depression of HDL levels. Coronary risk reduction has been disappointing when blood pressure has been lowered with treatment regimens based on thiazide diuretics and/or beta blockers. Thiazides and some beta blockers may further impair tissue insulin sensitivity and often cause blood lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia. 186 24

This review first summarizes evidence from animals and humans for and against a role for dietary sodium in the genesis and treatment of hypertension. The evidence for its role is strongest in those subjects with impaired ability to excrete sodium because of organic renal disease or mineralocorticoid excess. Here, restriction of dietary sodium promptly lowers pressure. Its role in the genesis of essential hypertension is more controversial. Nevertheless, it appears that some patients with mild to moderate essential hypertension respond to moderate sodium restriction with a modest fall in pressure. This restriction also seems to reduce the amount of antihypertensive medication needed to keep pressure under control. Next, the mechanism of the pressure response to dietary sodium chloride is considered, with emphasis on potassium depletion and increased plasma levels of prohypertensive sodium pump inhibitor and antihypertensive atrial natriuretic peptide. The evidence for a primary role for dietary potassium in the genesis of hypertension then is summarized; certain subsets of subjects with a high incidence of hypertension also have a lower potassium intake. Some investigators have found that dietary potassium supplementation lowers pressure in established hypertension. This may result from natriuresis and from vasodilation subsequent to stimulation of Na+,K(+)-ATPase in vascular smooth muscle and adrenergic nerve terminals. After the role of dietary calcium is discussed, practical aspects of dietary sodium restriction and dietary potassium supplementation in the therapy for established hypertension are considered. The review concludes with comments on their possible roles in the prevention of hypertension.
Hypertension 1991 Nov
PMID:Roles of sodium, potassium, calcium, and natriuretic factors in hypertension. 193 82

Endogenous factors with biological and immunological activity similar to cardiac glycoside drugs (endogenous digitalis-like factors; EDLF) have been found in several tissues and body fluids of animals and humans. Detectable EDLF concentrations were found in blood and urine extracts of adults (normal healthy controls, hypertensive patients and salt-loaded healthy subjects), while higher levels were generally observed in plasma samples of pregnant women, newborns, and patients with renal insufficiency. The chemical characteristics of this endogenous factor are, at present, unknown, although it has been suggested that EDLF could be a substance with low molecular weight. Experimental studies and theoretical considerations suggest that EDLF, in addition to the ability to react with antibodies, might also bind to the specific cellular receptor of the cardiac glycosides and thus inhibit the membrane Na+/K(+)-ATPase (sodium pump). Therefore, it has been suggested that EDLF is an endogenous modulator of the membrane sodium-potassium pump, and that it could play a role in the regulation of fluids and electrolytes, in the myocardial muscular tone and also in the pathogenesis of hypertension.
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PMID:Endogenous digitalis-like factors: their possible pathophysiological implications with particular regard to the perinatal period. 196 38

The sodium- and potassium-dependent adenosine triphosphatase (Na+,K(+)-ATPase) maintains the transmembrane Na+ gradient to which is coupled all active cellular transport systems. The R and S alleles of the gene encoding the Na+,K(+)-ATPase alpha 1 subunit isoform were identified in Dahl salt-resistant (DR) and Dahl salt-sensitive (DS) rats, respectively. Characterization of the S allele-specific Na+,K(+)-ATPase alpha 1 complementary DNA identified a leucine substitution of glutamine at position 276. This mutation alters the hydropathy profile of a region in proximity to T3(Na), the trypsin-sensitive site that is only detected in the presence of Na+. This mutation causes a decrease in the rubidium-86 influx of S allele-specific sodium pumps, thus marking a domain in the Na+,K(+)-ATPase alpha subunit important for K+ transport, and supporting the hypothesis of a putative role of these pumps in hypertension.
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PMID:Alteration of alpha 1 Na+,K(+)-ATPase 86Rb+ influx by a single amino acid substitution. 197 5

The effect of betamethasone on choroid plexus transport and CSF formation in rabbits was studied. Following 5 days of daily treatment with betamethasone the CSF production rate was reduced by 43% as measured by ventriculo-cisternal perfusion with radioactive inulin. Accordingly, the Na(+)-K(+)-ATPase activity and the transport capacity in the choroid plexus, measured in terms of choline (10(-5) M) uptake and accumulation in vitro, decreased (in the lateral ventricles by 31% in both cases). Isolated choroid plexuses from rabbits were also used to determine uptake and accumulation of choline and the activities of various types of ATPases following pretreatment of the animals with 17-beta-oestradiol, alone or in combination with progesterone. The combined treatment reduced the choline uptake by 35% and also lowered the activity of Na(+)-K(+)-ATPase by 31% without influencing tissue wet weight. Thus, the demonstrated influences of glucocorticoids and sex steroids on the transport capacity in the choroid plexus seem to be important components in their postulated effects on intracranial hypertension.
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PMID:Actions of sex steroids and corticosteroids on rabbit choroid plexus as shown by changes in transport capacity and rate of cerebrospinal fluid formation. 197 49

The relation between sodium and blood pressure is a centuries-old question. A substantial body of epidemiological and experimental data has accumulated that strongly implicates NaCl as having a causal role in the genesis of arterial hypertension. Prospective studies that have been performed in diverse populations that have manipulated NaCl exposure by diet or infusion have repeatedly documented an NaCl pressor effect. Further, similar studies in biracial populations have also demonstrated a greater prevalence of "salt sensitivity" in blacks compared with whites. The reasons for this observation are not entirely clear; however, intrinsic or hypertension-induced renal abnormalities that limit natriuretic capacity, reduced Na+,K(+)-ATPase pump activity, other membrane ion transport disturbances, differential exposure to psychological stressors, greater insulin resistance, and dietary factors (reduced Ca+ and K+ intake) have all been suggested as possibly playing a role. Salt sensitivity appears to be a widespread phenomenon. However, it is critically important to determine what factors account for racial differences in salt sensitivity. Moreover, the prevalence of salt sensitivity in the general population is unknown. Current definitions of salt sensitivity are varied and unidirectional. In comparison with bidirectional criteria (blood pressure increase with salt loading and blood pressure decrease with salt restriction), they are probably inadequate to identify salt-sensitive individuals who manifest less extreme blood pressure change after dietary sodium or plasma volume manipulations. More sensitive criteria for diagnosing salt sensitivity will facilitate a better understanding of racial and ethnic differences in the prevalence of salt sensitivity.
Hypertension 1991 Jan
PMID:Racial and ethnic modifiers of the salt-blood pressure response. 198 88

The genetic and cultural heritability and intercorrelation of traits related to hypertension have been carried out in 98 Utah pedigrees (2,500 person) and 58 sibships with two or more hypertensive persons (131 hypertensive persons). Although none of these traits has been established as a marker for "sodium-sensitive hypertension," many of them are related at least indirectly to both electrolyte metabolism and risk of hypertension. Significant recessive monogenic effects and high total heritability (52-84%) were found for urinary kallikrein, high fat pattern index, intraerythrocytic sodium, Na-Li countertransport, and ouabain binding sites. Familial correlations more strongly attributable to shared environment than to genetic effects were found for Na,K-ATPase pump activity, intraerythrocytic magnesium, plasma digoxin-like factor, plasma renin activity, and plasma sodium concentration. All anthropometric variables tested showed highly significant genetic heritability with low and insignificant shared family environmental effects. Several of the genetically determined cellular cation tests also correlated with other genetic traits including plasma lipids, anthropometric measurements, and other cellular cation tests. Among hypertensive individuals with familial dyslipidemic hypertension, plasma insulin levels correlated with obesity and lipid abnormalities and with several cellular cation flux tests associated with hypertension.
Hypertension 1991 Jan
PMID:Genetic traits related to hypertension and electrolyte metabolism. 198 14

After myocardial infarction in rats, muscle performance in the remaining hypertrophied myocardium deteriorates and is associated with a decrease in myosin adenosinetriphosphatase (ATPase) activity and a shift to the V3 myosin heavy-chain isoform. We have previously shown in another model of hypertrophy, secondary to renovascular hypertension, that chronic intermittent adrenergic stimulation with dobutamine (Db) can prevent this biochemical adaptation. The present study was undertaken to assess the effects of chronic Db treatment on cardiac mass, function, metabolism, and myosin biochemistry in animals subjected to chronic myocardial infarction. Four groups of rats were studied: controls, animals treated with Db (2 mg/kg 2X daily for 4 wk), animals subjected to myocardial infarction and killed after 4 wk (MI), and MI animals concurrently treated with Db for 4 wk (MI-Db). The two MI groups were subdivided into those with and without congestive heart failure (CHF). Heart weight was increased by 13% with Db, unchanged in the infarct groups without CHF, and increased by 9 and 22% in the infarct groups with CHF. Db did not have any additional effect on heart weight in these later groups. Infarct weight was greatest in the animals with CHF, and viable myocardium was equivalent in all infarct groups suggesting that CHF was associated with a greater degree of hypertrophy. Ventricular performance, as assessed in an isovolumic heart apparatus, was markedly depressed in both infarct groups with CHF and was not affected by Db. Db increased myosin ATPase activity in control and infarcted animals both with and without congestive heart failure. Myosin oxygen consumption and lactate production were not adversely affected by Db.
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PMID:Effects of chronic dobutamine on cardiac mechanics and biochemistry after myocardial infarction in rats. 199 90

Hypertension in insulin resistance states is generally attributed to hyperinsulinemia, with resulting increases in renal sodium retention and/or sympathetic nervous system activity. However, recent data from our laboratory suggest that cellular insulin resistance, rather than hyperinsulinemia per se, may lead to hypertension. The basic tenet proposed in this review is that the common mechanism involved in the development of hypertension in both type I and type II diabetes mellitus is a deficiency of insulin at the cellular level. Recent observations suggest that impaired cellular response to insulin predisposes to increased vascular smooth muscle (VSM) tone (the hallmark of hypertension in the diabetic state). For example, recently reported studies from our laboratory demonstrate that insulin in physiological doses attenuates the vascular contractile response to phenylephrine, serotonin, and potassium chloride. Thus, insulin appears to normally modulate (attenuate) VSM contractile responses to vasoactive factors, and insulin resistance should accordingly be associated with enhanced vascular reactivity. Abnormal VSM cell calcium [Ca2+]i homeostasis may be the nexus between insulin resistance and increased VSM tone. The genetically obese, hyperinsulinemic, insulin-resistant Zucker rat demonstrates increased vascular reactivity, reduced membrane Ca2(+)-ATPase activity, increased cellular Ca2+ levels, and a marked impairment in vascular smooth muscle Ca2+ efflux compared to lean controls. Insulin stimulates membrane Ca-ATPase, blocks Ca2+ currents, and Ca2(+)-driven action potentials. Thus, an insulin-resistant state as exists in the Zucker rat may be associated with increased Ca2+ influx through voltage-dependent sarcolemmal Ca2+ channels and/or decreased production or activation of the VSM cell Ca-ATPase pump.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of hypertension in diabetes. 202 49

The pathophysiology of hypertension in the black population differs to some extent from that of the nonblack population. Although black hypertensives exhibit enhanced sodium retention, expanded plasma volume, lower plasma renin activity, and a greater increase in blood pressure in response to high levels of Na+ intake compared with nonblack hypertensives, there is considerable heterogeneity in these studies. Alterations in ion transport mechanisms, such as a decrease in Na+K(+)-ATPase activity and Na+K+ cotransport, have been demonstrated in the black hypertensive population. Those features provide the physiologic basis for the differential response to monotherapy with diuretics and, perhaps, with calcium channel blockers, that is observed in black hypertensives, particularly when compared with responses to beta-blockers or angiotensin converting enzyme inhibitors.
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PMID:Pathophysiology of hypertension in blacks. 207 24


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