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)

In the inbred Dahl salt-sensitive rat (SS/Jr strain), it has been proposed that a T for A transversion in the DNA sequence encoding amino acid 276 in the alpha 1 subunit isoform of Na+,K(+)-ATPase may impair ion transport and contribute to the pathogenesis of hypertension. This hypothesis is of major scientific interest because it represents the first attempt to explain the pathogenesis of salt-sensitive hypertension on the basis of a specifically defined mutation at the DNA level. We devised a polymerase chain reaction technique to screen the genomic DNA of multiple SS/Jr rats for the T for A transversion reported in the complementary DNA (cDNA) encoding the alpha 1 subunit of Na+,K(+)-ATPase. When eight Dahl SS/Jr rats from Harlan Sprague Dawley Inc. were tested with the polymerase chain reaction technique, we found no evidence of this mutation in the Na+,K(+)-ATPase gene. Direct sequence analysis of the gene in three SS/Jr rats also did not show the T for A transversion. These results 1) strongly suggest that commercially available Dahl SS/Jr rats do not carry a T for A transversion in the genomic DNA sequence encoding amino acid 276 in the alpha 1 subunit isoform of Na+,K(+)-ATPase and 2) raise the possibility that the previous finding of a mutation in the cDNA of the SS/Jr rat may have been due to a reverse transcriptase error during cDNA synthesis.
Hypertension 1991 Nov
PMID:Sequence analysis of the alpha 1 Na+,K(+)-ATPase gene in the Dahl salt-sensitive rat. 131 80

We have previously reported that myocardial microsomal Na+,K(+)-ATPase activity, arterial wall ouabain-sensitive 86Rb uptake, and arterial smooth muscle cell membrane potentials are decreased and plasma Na(+)-K+ pump inhibitory activity is increased in rats during the fifth week of one-kidney, one-clip hypertension. We here report measurements of these four parameters and blood pressure following unclipping. A new series of rats with one-kidney, one-clip hypertension was prepared. Each animal was paired with a one-kidney, sham-clipped (nonconstricting clip) control rat. After 5 weeks, the clips were removed. In the hypertensive animals arterial pressure promptly (within 3 h) returned to normal and remained at the level for 7 observation days. On the third day following unclipping, all four parameters were not significantly different from those in the paired control animals. On the seventh day following unclipping, three of the four parameters were not significantly different from those in the paired control animals and arterial ouabain sensitive 86Rb uptake was slightly increased relative to the value in the control animals. These studies invite further inquiry into the possible role of plasma Na(+)-K+ pump inhibitory activity in the genesis and maintenance of the hypertension in this model.
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PMID:Reversal of one-kidney, one-clip hypertension in rats. Effects on myocardial Na+, K(+)-ATPase, arterial Na(+)-K+ pump, arterial membrane potential, and plasma Na(+)-K+ pump inhibitory activity. 166 Feb 80

Abnormalities in cardiovascular Na,K-ATPase ion-transport function and regulation may play an important role in the pathogenesis of hypertension. However, it is not known whether these abnormalities are secondary to the effects of hypertension, such as increased pressure, or reflect an intrinsic abnormality in Na,K-ATPase gene expression and regulation. A genetic model of hypertension was used to address this issue. Na,K-ATPase alpha subunit gene expression in hearts was compared between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Pre-hypertensive, 4-week old SHR hearts exhibited an approximately 4 fold elevation in alpha 1 and 8 fold elevation in alpha 2 mRNA levels compared with age-matched WKY hearts. These SHR mRNA levels remained almost equivalent throughout the development of hypertension at 8 and 16 weeks of age. WKY alpha 1 and alpha 2 mRNA levels exhibited a progressive increase during the same time period. The neonatal alpha 3 mRNA isoform was detected only in pre-hypertensive (4-week) SHR hearts. We conclude that cardiac Na,K-ATPase alpha subunit gene expression is significantly altered in SHR even before the onset of hypertension. These findings suggest that an abnormality in cardiac Na,K-ATPase gene expression constitutes an early, if not primary, event in spontaneous hypertension.
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PMID:Augmented Na,K-ATPase gene expression in spontaneously hypertensive rat hearts. 166 23

Milan hypertensive (MSH) rats develop hypertension around the 3rd-4th week of life and exhibit increased Na-pump activity in adulthood. The present study was performed to evaluate whether or not hypertension is preceded by an increase in Na-K-ATPase activity. Total and ouabain-sensitive ATPase activities were studied in single microdissected medullary thick ascending limb of Henle (mTAL) tubules from MHS, Milan normotensive (MNS) and Sprague-Dawley (SD) rats at 22-24, 26-28 and 45-60 days of age. Data are given as mean +/- SEM. Total and Na-K-ATPase activity exhibited a developmental pattern in MHS, MNS and SD rats. At 22-24 days no difference was seen between MHS and MNS animals. At 26-28 days MHS had a higher total and Na-K-ATPase activity than MNS (3031 + 171 vs 2471 + 178 pmol phosphate/mm tubule per hour, P less than 0.05; 2289 + 205 vs 1653 + 151, n = 10, P less than 0.05). At this age there was still no difference in mean arterial blood pressure (88 + 4 vs 86 + 3 mm Hg, n = 15). Adult MHS rats had higher blood pressure (140 + 9 vs 112 + 8 mm Hg, P less than 0.001) and higher total (3544 + 136 vs 2718 + 215 pmol phosphate/mm tubule per hour, n = 10, P less than 0.01) and Na-K-ATPase activity (2670 + 99 vs 1942 + 217 pmol phosphate/mm tubule per hour, n = 10, P less than 0.05) than adult MNS rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased renal tubular Na-K-ATPase activity in Milan hypertensive rats in the prehypertensive period. 166 81

Digitalis-like substance (DLS) was measured by Na-K-ATPase inhibitor (ATPI) activity and digitalis-like immunoreactivity (DLI) in 100 patients with type II diabetes. Hypertensive diabetic patients with a positive family history for hypertension had high ATPI levels compared with those patients with a negative family history for the disease. DLI level did not differ between groups. There was no significant difference in ATPI and DLI levels among three groups based on level of urinary albumin excretion. These data suggest that a circulating factor (or circulating factors) determined by ATPI may be linked with genetic factors in the development of hypertension, but not to the development of diabetic nephropathy.
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PMID:Elevated endogenous Na-K-ATPase inhibitor activity in hypertensive diabetic patients with a family history of hypertension. 166 15

1. The contractile responses of aortic ring preparations from Sprague-Dawley rats made hypertensive by 6-week dietary salt loading were studied. The test and control diet contained 8.0 and 0.3% NaCl, respectively. Aortic rings from salt-loaded rats showed enhanced sensitivity to noradrenaline (NA) but not to serotonin. Contractile responses to CaCl2 in Ca-free NA-containing medium was significantly enhanced in salt-loaded rats, but was unchanged in K(+)-depolarised medium. K(+)-induced relaxation (a functional indicator of Na-K adenosine triphosphatase activity) was sensitive to 10 mumol/L ouabain and was significantly attenuated in aortic rings from salt-loaded rats. The results suggest that hypertension induced by salt-loading is associated with enhanced sensitivity to NA, increased Ca2+ entry through receptor-operated channels, and impairment of Na-K ATPase enzyme activity.
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PMID:Altered responses of aortic smooth muscle from Sprague-Dawley rats with salt-induced hypertension. 166 59

To estimate the participation of a Na+,K(+)-ATPase-inhibiting plasma factor in pregnancy induced hypertension (PIH), the inhibitory activity and the characteristics of plasma extract eluted with ethanol through a C8 column were examined in normotensive non-pregnant women (N) and women with normal pregnancy (NP) and PIH. There were no differences among the 3 groups in the Na+,K(+)-ATPase activity of erythrocyte ghosts. The heat- and acid-stable plasma extract dose-dependently inhibited Na+,K(+)-ATPase activity with a pattern similar to that of ouabain, but different from that of vanadate. The inhibitory activity of plasma extract was not influenced by polyclonal digoxin antibody which almost completely prevented digoxin-induced inhibition and slightly but significantly reduced the ouabain-induced one. The results indicate that the plasma extract has ouabain-like inhibitory activity on Na+,K(+)-ATPase and that it is not endogenously synthesized digoxin itself, but a substance differing in structure from digoxin. Furthermore, the ouabain-like Na+,K(+)-ATPase inhibitory activity in NP plasma was significantly lower than that in PIH plasma, which was similar to that in N plasma. There were significant relationships between the ouabain-like Na+,K(+)-ATPase inhibitory activities in plasma and the diastolic and systolic blood pressures in NP and PIH groups. The results suggest that the lower ouabain-like Na+,K(+)-ATPase inhibitory activity in plasma probably participates in maintaining the blood pressure within the normal range during pregnancy and its failure may be involved in the genesis of PIH.
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PMID:Ouabain-like Na+,K(+)-ATPase inhibitory activity of a plasma extract in normal pregnancy and pregnancy induced hypertension. 166 21

The activity and properties of Na,K-ATPase in erythrocytes and their membrane preparations (ghosts) from 34 subjects with borderline hypertension and 21 normotensive controls were studied. The Na,K-ATPase activity was found to be by 43% lower as compared to control group. No changes in the Na,K-ATPase activity were revealed in the ghosts of borderline subjects. This suggests that the plasma of borderline subjects contains an inhibitor of Na,K-ATPase. The plasma level of sodium pump inhibitor was measured in 21 borderline hypertensive subjects. It was found to be about 19% compared with the control group. These findings suggest presence of Na,K-ATPase inhibitor in the plasma of borderline subjects, which is likely to be involved in the development of hypertension.
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PMID:[The activity and properties of Na,K-ATPase in the erythrocytes and the Na-pump inhibitor in the plasma of subjects with borderline arterial hypertension]. 166 9

In the present work we reported the results of the study of erythrocyte membrane Na+,K(+)-adenosine triphosphatase (ATPase) and Mg(2+)-ATPase in patients with essential hypertension and controls. In the 40 patients with hypertension, a more marked decrease of Na+, K(+)-ATPase was observed. The behavior of the enzyme at Mg2+ activation, ouabain inhibition and the response to different temperature suggest the possibility of differences between the two groups. The normal erythrocyte Mg(2+)-ATPase activity in two groups suggest also the possible role of ratio Na+, K(+)-ATPase/Mg(2+)-ATPase in the study of essential hypertension. However the relevance of magnesium and Mg(2+)-ATPase to the pathogenesis of essential hypertension remains unclear but merits further study. On the basis of these considerations the aim of the present study was to identify, in a kinetic approach, the presence of different abnormalities of Na+ transport and Na+, K(+)-ATPase in erythrocytes from patients with essential hypertension. Much evidence has supported the hypothesis that essential hypertension is a heterogeneous disease in the pathophysiological mechanisms as well as in its clinical and therapeutical consideration.
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PMID:[Various properties of the Na+, K(+)-ATPase and the Mg (2+)-ATPase in erythrocytes from normotensive and hypertensive subjects]. 166 78

Dopamine receptors of DA-1 and DA-2 subtypes are localized in various regions within the kidney including the renal vasculature (DA-1) as well as sympathetic nerve terminals innervating the renal blood vessels (DA-2). More recent studies using receptor-ligand binding and receptor autoradiography have shown that DA-1 receptors are localized at both the luminal and basolateral membranes at the level of the proximal tubules. Activation of these DA-1 receptors by dopamine and by selective DA-1 receptor agonists results in natriuresis and diuresis. The cellular signaling mechanisms responsible for this response appear to be DA-1 receptor-induced activation of adenylate cyclase and phospholipase C, which via the generation of various intracellular messenger systems cause inhibition of Na(+)-H+ antiport (luminal) and Na+, K(+)-ATPase (basolateral), respectively. Both of these events consequently inhibit sodium reabsorption leading to natriuresis and diuresis. It is also known that dopamine can be synthesized within proximal tubular cells from L-dopa, which is taken up from the tubular lumen, and this locally produced dopamine plays an important role in the regulation of sodium excretion particularly during increases in sodium intake. Furthermore, a defect in the renal dopaminergic mechanism may be one of the pathogenic factors in certain forms of hypertension. Finally, whereas DA-1 receptor agonists are shown to be of therapeutic benefit in the treatment of hypertension, heart failure, and acute renal failure, some selective DA-2 receptor agonists are effective antihypertensive agents.
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PMID:Anatomical distribution and function of dopamine receptors in the kidney. 168 44


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