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)

To explore the etiology of altered Ca metabolism in essential hypertension, we studied parameters, i.e., maximal initial reaction velocity (Vmax) and Michaelis constant (Km), of Ca activation kinetics of Ca2(+)-ATPase in membrane fractions (isolated by a sucrose gradient) from platelets of blacks and whites, 27 of whom were essential hypertensives, 17 of whom were normotensives with a family history of essential hypertension, and 10 of whom were normotensives without a family history of the disease. The Vmax of hypertensives was significantly lower than in normotensives without a family history of essential hypertension (hypertensives, 14.99 +/- 1.71 nmol Pi.mg protein-1.min-1; normotensives, positive family history, 22.67 +/- 3.17 nmol Pi.mg protein-1.min-1; normotensives, negative family history, 27.54 +/- 4.37 nmol Pi.mg protein-1.min-1; overall, P = 0.0078). The Km was lower in both hypertensives and normotensives with a positive family history of essential hypertension as compared with normotensives with a negative family history of the disease (hypertensives, 1.70 +/- 0.23 microM; normotensives, positive family history, 1.38 +/- 0.2 microM; normotensives, negative family history, 2.79 +/- 0.58 microM; overall, P = 0.0251). Furthermore, the Km in whites was inversely related to plasma renin activity (r = 0.50; P less than 0.005). We propose that a lower Vmax for Ca2(+)-ATPase may play a role in the higher level of free Ca in platelets of essential hypertensives and that a higher affinity of the enzyme to Ca may reflect a process compensating for the lower Vmax. We also suggest that a higher Km for Ca2(+)-ATPase in juxtaglomerular cells of whites would result in blunting the release of renin.
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PMID:Kinetics of Ca2(+)-ATPase activation in platelet membranes of essential hypertensives and normotensives. 214 60

Calpain, a calcium-dependent, neutral cysteine-protease was purified from the erythrocyte cytosol of subjects having essential hypertension (HTN), sickle cell anaemia, (SCA), or kwashiorkor (KWA). Identical electrophoretic mobility on SDS-polyacrylamide gradient gel, sensitivity to micromolar amounts of Ca2+, absolute requirement for a reducing environment and a high susceptibility to inhibition by leupeptin and thiol-group modifying reagents confirm that calpain preparations from these erythrocytes are equivalent to calpain I. Whereas the extent of calpain activation of erythrocyte membrane Ca2(+)-pumping ATPase of normal subjects was almost equal to that due to calmodulin, calpain activation of the HTN and SCA pump was greater than activation by calmodulin. Like in normal membranes, exogenous calmodulin protected the Ca2(+)-pumping ATPase of these erythrocytes against calpainization; the degree of protection by calmodulin is least in SCA and HTN. Electrophoretic separation of erythrocyte membranes and the purified Ca2(+)-pumping ATPase of HTN, SCA and KWA subjects does not indicate the presence of fragments resulting from the proteolytic action of calpain.
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PMID:Comparative action of calpain on erythrocyte Ca2(+)-pumping ATPase in sickle cell anaemia, essential hypertension and kwashiorkor. 214 87

The Ca2(+)-ATPase activity and calmodulin (CaM) of erythrocytes and the effect of nifedipine on them were studied in subjects with essential hypertension (EHT). The results showed that both the basal and maximal Ca2(+)-ATPase activities of erythrocytes were lower in subjects with EHT than those in normal controls, and Ca2+a-ATPase activities were negatively correlated with blood pressure; the content of CaM was also reduced, and it was positively correlated with maximal Ca2(+)-ATPase activity. The basal Ca2(+)-ATPase activity was improved with nifedipine, but the maximal Ca2(+)-ATPase activity and CaM content were both unchanged significantly. Thus, the Ca2(+)-ATPase and CaM of erythrocytes might play an important role in EHT, and nifedipine has a mild effect on cellular calcium transporting.
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PMID:[Changes of Ca2(+)-ATPase and calmodulin in erythrocytes and their responses to nifedipine in essential hypertension]. 215 Aug 3

To clarify the role of Na,K-ATPase inhibitor in the enhanced pressor response to infused noradrenaline (NA-R) in patients with benign essential hypertension (EHT), NA-R, plasma noradrenaline concentration (PNA), and blood ionized calcium (Ca2+) were investigated before and after intravenous injection of ouabain in 15 normotensive subjects (NT) and 13 EHT. NA-R was enhanced by ouabain in both NT and EHT. The augmentation of NA-R following ouabain injection (delta NA-R) and % delta NA-R were significantly lower in EHT than in NT. Following ouabain injection, no significant change in PNA and blood Ca2+ was observed in both NT and EHT. NA-R negatively correlated with PNA and blood Ca2+, which were estimated just prior to noradrenaline infusion, before ouabain injection as well as after. After ouabain, the regression line between NA-R and PNA or blood Ca2+ shifted toward higher NA-R level in NT, unlike in EHT. These results suggest that an exogenous Na,K-ATPase inhibitor brings about a blunted enhancement of NA-R in EHT consistent with the presence of an endogenous Na,K-ATPase inhibitor in EHT.
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PMID:The role of Na,K-ATPase inhibitor on pressor responsiveness in patients with benign essential hypertension. 215 65

Despite the fact that numerous studies have been published regarding the possible presence in plasma of an endogenous Na-K pump inhibitor with a digitalis-like structure in essential hypertension, very little is known about this factor in heart disease in general, and in situations characterized by low cardiac output. We measured the ability of plasma obtained from the femoral vein to inhibit a human renal Na(+)-K+ ATPase before and immediately after percutaneous transluminal coronary angioplasty (PTCA) in 6 patients suffering from angina pectoris and severe coronary stenosis. Intraerythrocyte sodium and potassium concentrations were also measured simultaneously. Na(+)-K+ ATPase inhibition proved significantly greater after angioplasty as compared to basal activity (percentage inhibition: 31.5 +/- 7.8 vs 16.1 +/- 12.2). No significant changes in intraerythrocyte sodium and potassium were detected. Though we are not in a position to define the mechanism underlying the increase in the digitalis-like factor, a plausible hypothesis may be that the reduction in cardiac output during PTCA by raising cardiac pressures may stimulate the production of a factor of compensatory inotropic significance.
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PMID:Increase in plasma digitalis-like activity during percutaneous transluminal coronary angioplasty in patients with coronary stenosis. 216 10

1. We have measured the effect of oral salbutamol on cation transport in vivo by studying the disposition of an oral load of rubidium chloride in healthy treated volunteers and in untreated matched controls. 2. During the administration of salbutamol there was a significantly lower plasma rubidium concentration 5 h after the administration of the oral load of rubidium chloride, reflecting an increase in the net clearance of rubidium from the plasma into at least some tissues in vivo. 3. There was no difference in either intraerythrocytic rubidium concentrations or the pseudo-rate constant for erythrocyte rubidium uptake in vivo after salbutamol. 4. Ex vivo incubation of whole blood preloaded in vivo with rubidium showed that the clearance of rubidium from the plasma was inhibited by 95% in the presence of the Na+,K(+)-ATPase inhibitor digoxin. 5. These data suggest that salbutamol stimulates cation transport via Na+,K(+)-ATPase in vivo into some tissues but not into the erythrocyte. 6. This pattern of change in rubidium disposition after salbutamol is completely different from the patterns of change we have seen in patients with essential hypertension or acute manic illness. We therefore suggest that the changes in erythrocyte rubidium uptake which we have previously described in vivo in patients with essential hypertension or acute manic illness do not result from beta 2-adrenoceptor-mediated catecholamine stimulation of Na+,K(+)-ATPase.
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PMID:The effect of oral salbutamol on cation transport measured in vivo in healthy volunteers. 217 17

The presence of an endogenous ouabain-like substance in bovine hypothalamus is demonstrated on the bas is of the ability of acid acetone extracts of hypothalamus to inhibit (NA+ + K+)-ATPase activity, 86Rb uptake, 22Na efflux and (3H)ouabain binding. Partial purification of the substance was achieved by acetic acid fractionation followed by sephadex-G25 chromatography and subsequent desalting by mixed-bed resin. The results are discussed with relation to the important role of the sodium pump inhibitor in the regulation of (N+ + K+)-ATPase activity and sodium transport and hence in the pathophysiologic mechanisms of essential hypertension.
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PMID:[(NA++K+)-ATPase inhibitor from bovine hypothalamus]. 217 83

Racial differences in the regulation of Na+, K+, and Ca2+ have been shown both at the systemic and cellular levels. These include a higher incidence of "salt sensitivity," lower urinary K+ excretion, lower plasma renin activity, and higher circulating levels of immunoreactive parathyroid hormone and 1.25 dihydroxyvitamin D in blacks than in whites. Blacks exhibit a higher erythrocyte Na+ concentration, coupled with a lower maximal initial reaction velocity of erythrocyte Na,K-ATPase. Blacks also appear to differ from whites in erythrocyte Na+, K+ cotransport and Na-Li countertransport. Moreover, they show a higher activity of the Na(+)-H+ antiport in skin fibroblasts and a greater response of cellular Ca2+ signaling to agonists in serum. Mechanisms linking some of these racial differences in ionic metabolism to the increased propensity of blacks to develop essential hypertension are proposed, and the epidemiology and characteristics of this disease in blacks are reviewed.
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PMID:Essential hypertension in blacks: epidemiology, characteristics, and possible roles of racial differences in sodium, potassium, and calcium regulation. 217 6

Thiazide diuretics are particularly efficacious in the treatment of hypertension in blacks. A number of observations suggest that many hypertensive blacks have features consistent with a status of "corrected" volume expansion. Our studies, as well as those of other investigators, show that the Na,K pump is inhibited in leucocytes and erythrocytes of blacks with essential hypertension. This observation is also consistent with the concept of volume expansion in hypertensive blacks, since the Na,K pump is inhibited in many forms of experimental volume expansion, including the administration of salt in normal humans. We postulate that the efficacy of thiazide diuretics may be related to their ability to stimulate the Na,K pump. We present data obtained in 13 black hypertensive men in whom Na efflux, and Na,K-ATPase in the erythrocyte rose significantly after 7 days of treatment with hydrochlorothiazide, 50 mg/day. Diuretic therapy may indirectly result in reduced intracellular calcium in the vascular smooth muscle.
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PMID:Diuretics and cation transport in hypertensive blacks. 217 10

Overall, there is agreement that the origins of hypertension have a genetic basis. The genetic factors interact with environmental factors that influence expression and intensity of the disorder. As summarized in Table 1, there is evidence from the literature to identify pathways for the development of hypertension in blacks. Organ pathology, characteristic of the clinical phenotypic hypertension, consists of increased peripheral vascular resistance and left ventricular hypertrophy, and, particularly in blacks, nephrosclerosis. In this scheme, an intermediate phenotype is a biochemical or endocrine marker of gene expression that participates in the regulation of blood pressure. Intermediate phenotypic characteristics of essential hypertension include sodium sensitivity, adrenergic activity, cation transport, and endocrine function including renin-angiotensin-aldosterone, kallikrein-kinin, and prostaglandin. Another intermediate phenotype to be included in this discussion is insulin resistance. These intermediate phenotypes of cell and subcellular function are regulated by candidate genes. Alternatively, an intermediate phenotype can be expressed in response to another intermediate phenotype. For example, sodium sensitivity could be mediated by the cation transport mechanism of Na,K-ATPase, or insulin resistance could be induced by an elevated level of adrenergic activity. Gene expression of the intermediate phenotype is also modulated by environmental factors such as dietary sodium, potassium, or calcium, and social stresses or patterns of physical activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differences in blacks and whites with essential hypertension: biochemistry and endocrine. State of the art lecture. 219 Sep 20


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