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

Increasing experimental evidences suggest an involvement of an endogenous Na+/K+ ATPase inhibitor in regulating water and electrolytes balance as well as in the pathogenesis of hypertension. However, conflicting results on the nature and the chemical structure of this substance still make it difficult to understand exactly its physiological mechanism of action. In the present study an attempt was made to purify a Na+/K+ ATPase inhibitor from hypertensives' plasma by solid phase extraction followed by 2 HPLC steps using reverse and normal phase columns. The fractions, from both columns, were able to inhibit Na+/K+ ATPase, 3H-ouabain binding to enzyme, ouabain sensitive 86Rb uptake and pNPPase activity in a manner not affected by boiling. Ultrafiltration experiments demonstrate that inhibitory activity is largely due to a low-molecular weight substance. These findings seem to confirm the presence in hypertensives plasma of a Na+/K+ ATPase inhibitor with some similarities with ouabain.
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PMID:Purification of a Na+/K+ ATPase inhibitor from borderline hypertensives' plasma. 216 62

This ultracytochemical study was undertaken to determine whether increased arteriolar permeability in acute hypertension is accompanied by altered localisation of the ouabain-sensitive, K(+)-dependent p-nitrophenyl-phosphatase (K(+)-NPPase), a component of the Na+, K(+)-ATPase system. Rats were injected with horseradish peroxidase (HRP) intravenously and acute hypertension was induced by a 2-min infusion of angiotensin amide. Rats were killed at 3 and 15 min, following which brains were sliced and reacted for demonstration of K(+)-NPPase and HRP reaction product. Vessels of normotensive and hypertensive rats that were nonpermeable to HRP showed discontinuous distribution of K(+)-NPPase on the outer plasma membranes of endothelial and adventitial cells of arterioles and endothelial cells and pericytes of capillaries. Arterioles of the hypertensive rats which were permeable to HRP showed marked reduction of K(+)-NPPase localisation in their walls at 3 min while at 15 min when the blood pressure had returned to resting levels the enzyme localisation was similar to controls. This study demonstrates transient alteration of the NA+, K(+)-ATPase system during increased endothelial permeability in acute hypertension. The implication of this finding and our previous observation of reduced Ca2(+)-ATPase localisation in endothelial plasma membranes in acute hypertension has been discussed.
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PMID:Ultracytochemical localisation of Na+, K(+)-ATPase in cerebral endothelium in acute hypertension. 216 85

Inhibition of the Na(+)-K+ pump by digitalis compounds has been reported to increase intracellular Na+ and Ca2+ concentrations and to stimulate Na(+)-H+ exchange. The activity of endogenous digitalis-like compounds, proposed to promote natriuresis and to raise blood pressure, has been found to be increased in volume expansion and hypertension. The enhanced cytosolic [Ca2+] present in platelets from hypertensive patients may thus originate from inhibition of the Na(+)-K+ pump by endogenous inhibitors, enhanced mobilization of internal Ca2+ stores due to phospholipase C activation and/or structural membrane defects. In unstimulated platelets from essential hypertensives, the increase in [Ca2+]i depends on external Ca2+, thereby underlining the importance of Ca2+ influx. The observation that [Ca2+]i was also enhanced in erythrocytes (p = 0.03) demonstrates that intracellular stores are not required for this rise. Plasma digitalis-like activity was positively correlated with platelet [Ca2+]i (inhibition of renal Na+,K(+)-ATPase, competition with ouabain binding, p less than 0.01). Platelet [Ca2+]i also rose during chronic digoxin administration (p less than 0.02) but not after acute in vitro ouabain treatment. The alkalinisation of platelet cytosol (p = 0.005) also agrees with the stimulation of the Na(+)-H(+)-exchange. In conclusion, these results are compatible with a participation of endogenous Na(+)-K+ pump inhibitors in the control of cytoplasmic [Ca2+] and cell excitability.
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PMID:Endogenous inhibitors of the Na+, K(+)-pump and platelet Ca2+ handling in hypertension. 216 68

The short term regulation of the activity of the Na,K-pump (Na+,K(+)-ATPase) is just beginning to be understood. By using single microdissected proximal tubule segments (PCT) (permeabilized in order to clamp Na entry), it was possible to study regulation of Na+,K(+)-ATPase activity in its own environment and in a well defined cell population. The Na+,K(+)-ATPase activity can be regulated over a short term via guanidine triphosphate (GTP) dependent regulatory proteins. However the guanidine proteins are not directly coupled to the Na,K-pump and the mechanism involves the activation of complex intracellular signalling system. Locally produced dopamine induces a dose dependent inhibition of Na+,K+ ATPase activity. This inhibition is mediated by a complex mechanism that requires the activation of both membrane dopamine receptors, DA-1 and DA-2. It involves the activation of a pertussis toxin sensitive GTP-binding protein and activation of protein kinase C. A DA-2 agonist only inhibits Na+,K(+)-ATPase activity when it is incubated together with dibutyryl cAMP or Forskolin. We have therefore concluded that an increase in cellular cAMP levels plays a permissive role for DA-2 inhibition of Na+,K(+)-ATPase activity. A fully differentiated cell is required for dopamine inhibition of Na+,K(+)-ATPase activity. An abnormal regulation of proximal tubule Na+,K(+)-ATPase activity might be of importance in the pathogenesis of certain types of hypertension.
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PMID:Short-term regulation of Na+,K(+)-ATPase activity by dopamine. 216 34

The effects of calcium and deoxycorticosterone (DOC) were studied in four groups of spontaneously hypertensive rats (SHR): control, calcium, DOC and DOC + calcium. Calcium was administered in drinking fluid as 1.5% calcium chloride, and DOC was injected weekly (25 mg/kg subcutaneously). During the 9-week study the increase in systolic blood pressure was enhanced in the DOC and attenuated in the calcium group, but did not differ from control values in the DOC + calcium group. DOC augmented in vitro contractions of aortic and mesenteric arterial rings induced by noradrenaline and impaired relaxations in response to nitroprusside and acetylcholine. Calcium alone enhanced the relaxation in response to nitroprusside in the mesenteric artery. In the DOC + calcium group vascular contractions did not differ from control values, but the relaxations caused by nitroprusside and acetylcholine were augmented in the mesenteric artery. The activity of erythrocyte Ca2(+)-ATPase increased in both calcium groups. The Na+:K+ ratio of tail artery tissue was reduced in the calcium group. In conclusion, calcium supplementation attenuates the development of hypertension, and prevents DOC-induced blood pressure increases in SHR by altering vascular reactivity. Changes in smooth muscle electrolyte ratios and Ca2(+)-ATPase activity may account for these alterations.
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PMID:Effects of a high calcium diet and deoxycorticosterone on vascular smooth muscle responses in spontaneously hypertensive rats. 217 73

Erythrocyte Na, K-ATPase was examined for its activity and relation to the concentration of the complexon EDTA in 39 patients with arterial hypertension (AH), 12 subjects with borderline hypertension, and 18 normotensives. The ionic composition and deformability of erythrocytes were also studied. As compared to normotensives, the patients with Stage I AH displayed a significantly lower activity of erythrocyte Na, K-ATPase, which may suggest that there is an enzyme inhibitor in the blood of the patients. According to the enzyme activity, the patients with Stage II AH were divided into two subgroups: 1) those with a lower activity and 2) those with a higher activity than healthy subjects. The patients with a Stage II AH who showed a lower activity of Na, K-ATPase exhibited a more elevated erythrocyte sodium level, whereas those who had a high activity of the enzyme displayed a decreased erythrocyte deformability. In addition, a positive correlation between erythrocyte sodium concentrations and Na, K-ATPase activity, as well as erythrocyte deformability was found in normotensives, whereas a negative correlation was established in AH patients.
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PMID:[Ionic homeostasis and erythrocyte deformability in patients with primary arterial hypertension]. 217 12

Increased renal nerve activity and sodium retention have been implicated in the development of hypertension in genetically transmitted forms of this disease. The present studies were designed to investigate the relationship between renal nerve integrity and renal proximal tubule (Na+, K+)-ATPase activity in spontaneously hypertensive rats (SHR). (Na+, K+)-ATPase activity of basolateral membranes (BLMs) enriched from proximal tubules of five-week-old SHR was greater, 328.6 +/- 18.9 nmol Pi/mg protein.min, than in age-matched genetic controls rats (Wistar-Kyoto, WKY, rats), 262.3 +/- 34.6 nmol Pi/mg protein.min (P less than 0.02). There was no detectable difference in (Na+, K+)-ATPase activity of 13-week-old SHR and WKY rats. Prior renal denervation was associated with a reduction in proximal tubule basolateral membrane (BLM) (Na+, K+)-ATPase activity, 316.8 +/- 23.8 to 223.1 +/- 23.9 nmol Pi/mg protein/min (P less than 0.02), in five-week SHR. However, denervation had no effect on renal (Na+, K+)-ATPase activity in either WKY rats, nor did sham-denervation in SHR. In addition, exogenous norepinephrine, 1 microM, produced a more pronounced stimulation of (Na+, K+)-ATPase activity in basolateral membranes from SHR as opposed to WKY controls (40.2% vs. 28.7%). Therefore, renal nerve integrity and exogenous catecholamines have a greater stimulatory influence on proximal tubule (Na+, K+)-ATPase activity in the early stages (prior to 5 weeks) of the development of hypertension in SHR than in age-matched WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adrenergic regulation of (Na+, K+)-ATPase activity in proximal tubules of spontaneously hypertensive rats. 217 14

In order to explain the opposite effect of 6,7-dihydroxylated isomers of 6, 7 - dihydrocanrenone on the urinary sodium and potassium excretion, we have tested the effect of these substances isolated from human urine on the Na(+)-K+ pump from different tissue preparation: rabbit kidney slices as well as NA-K ATPase purified from the kidney. Our results show an inhibition of pump as well as enzyme activity by the 6 beta 7 alpha isomer while the 2 other isomers are either uneffective or slightly stimulating. The 6 beta 7 alpha dihydroxy-6, 7-dihydrocanrenone could be one of the plasma ouabain-like substance incriminated in the pathogenesis of volume-expanded hypertension.
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PMID:[Arguments for the existence of an endogenous inhibitor of renal Na-K ATPase with steroid structure and natriuretic action]. 217 82

Sodium chloride has no clearly established local direct action on blood vessels to produce constriction; on the contrary, it has an immediate local indirect action via osmolality, which produces vasodilation. Thus in order to explain salt-induced hypertension, a delayed remote indirect vasoconstrictor action must be postulated. This indirect vasoconstrictor action is apparently the result of volume expansion. Acute volume expansion imparts three physiologic properties to the plasma; these are the ability to inhibit Na,K-ATPase and the Na-K pump, to cause natriuresis, and to sensitize blood vessels to vasoconstrictor agents. Similarly, low-renin, volume-expanded hypertension endows the plasma with the capacity to inhibit the Na,K-ATPase pump, to sensitize blood vessels to vasoconstrictor agents, and to raise blood pressure. These properties apparently result from a circulating digitalislike substance(s), perhaps derived from the hypothalamus and/or adrenals. We here review the considerable effort expended in identifying the agent or agents, and conclude that both steroidal and peptidic structure must be considered. Regardless of its structure, we hypothesize that when sodium excretion does not keep pace with sodium intake, its release leads to increased contractile activity of cardiac and vascular smooth muscle and hence hypertension. Inhibition of the Na-K pump increases the intracellular sodium concentration, particularly when superimposed on genetic- or aldosterone-induced increased sodium permeability, resulting in depolarization and increased calcium influx (vascular smooth muscle) or altered Na(+)-Ca2+ exchange and decreased calcium efflux (heart muscle). The increased intracellular calcium concentration then accounts for the increased contractile activity. Depolarization may also increase the sensitivity of vascular smooth muscle to vasoconstrictor agents such as norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Digitalislike circulating factor in hypertension: potential messenger between salt balance and intracellular sodium. 217 7

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


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