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

A circulating Na+, K+-ATPase inhibitor may cause arterial hypertension in patients with suppressed plasma renin activity, either directly or by sensitizing peripheral vessels to alpha-adrenergic stimulation. This hypothesis was tested by evaluating forearm arteriolar (plethysmographic technique) response to exogenous alpha-adrenergic stimulation by a 2-minute intra-arterial infusion of norepinephrine (0.1 microgram/dl tissue per minute) and to Na+, K+-ATPase inhibition by sequential 20-minute intra-arterial infusions of ouabain (0.36 and 0.72 microgram/dl tissue per minute). Two groups of hypertensive subjects with suppressed plasma renin activity, either essential or secondary to aldosterone excess, were compared with age-matched and sex-matched hypertensive subjects with normal plasma renin activity (n = 7 per group). No significant differences in forearm vascular response to norepinephrine were found among the three groups. Ouabain caused a highly significant, dose-related increment in forearm vascular resistance that was not accompanied by changes in the contralateral limb or systemic blood pressure. No significant interindividual differences in vascular responsiveness to ouabain were found. The individual increments in forearm vascular resistance during ouabain administration were unrelated to basal values or to plasma aldosterone, norepinephrine, or potassium concentrations. These data are not consistent with the hypothesis that suppressed basal Na+, K+-ATPase activity is primarily a characteristic of hypertensive patients with unresponsive plasma renin activity. Overall, these results cast doubts on the possibility of linking the development of human low renin hypertension to an endogenous Na+, K+-ATPase inhibitor.
Hypertension 1986 Sep
PMID:Vascular responses to ouabain and norepinephrine in low and normal renin hypertension. 301 54

Circulating inhibitor of Na+,K+-ATPase and ouabain-like immunoreactivity were studied in patients with essential hypertension. In the plasma of patients, two types of Na+,K+-ATPase inhibitors (ouabain-like and non-ouabain-like inhibitors) and ouabain-like immunoreactivity were detected. Ouabain-like inhibitor was clearly detected at a low KCl concentration (0.1 mM) in the assay buffer, and non-ouabain-like inhibitor was detected at a high KCl concentration (10 mM). The plasma level of ouabain-like inhibitor correlated significantly with that of ouabain-like immunoreactivity (p less than 0.001) and with a mean blood pressure (p less than 0.01). The plasma level of non-ouabain-like inhibitor was not correlated with the levels of either ouabain-like immunoreactivity or mean blood pressure. The level of plasma ouabain-like inhibitor did not correlate with that of plasma non-ouabain like inhibitor. Both ouabain-like inhibitor and ouabain-like immunoreactivity in the plasma of patients with essential hypertension were significantly higher than those in normotensive subjects, but the plasma level of non-ouabain-like inhibitor in patients with essential hypertension was not higher than that in normotensive subjects. These results suggest that the plasma from patients with essential hypertension contains ouabain-like factor(s) which is important to maintain the high blood pressure.
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PMID:Ouabain-like and non-ouabain-like factors in plasma of patients with essential hypertension. 304 Mar 6

Numerous studies have demonstrated that Na+/Li+ countertransport is increased in erythrocytes from hypertensive patients. Since Na+/Li+ countertransport is conducted through the physiologically occurring Na+/Na+ exchange, we studied the latter pathway in 20 subjects with essential hypertension and 20 normotensive subjects matched for age and sex. Ten hypertensives and six normotensives had a positive family history of hypertension. Ouabain (0.1 mM) and furosemide (0.1 mM) were used to assess the active Na+ efflux and Na+-K+-Cl- pathway. There was no significant difference between hypertensive and normotensive subjects in any of the three pathways studied. Among the 16 subjects with a positive family history of hypertension, the mean value for external Na+-dependent Na+/Na+ exchange was significantly higher than in 24 subjects with no family history of hypertension (0.0457 +/- 0.0337 versus 0.0283 +/- 0.0202; P less than 0.05). This study suggests that an inherited membrane transport defect may exist for Na+/Na+ exchange in families of hypertensive subjects.
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PMID:Relationship between red cell sodium transport, blood pressure, and family history of hypertension. 340 59

1. Essential hypertension is associated with increased intracellular sodium in both erythrocytes and leucocytes. Reports in the literature indicate that increasing the level of polyunsaturated fat in the diet reduces hypertension. In the present study, spontaneously hypertensive rats (Wistar-Kyoto, which develop systolic blood pressures in excess of 140 mmHg by 8 weeks of age) were fed on high-fat diets (40% energy derived from fat), the fat being maize oil (high in polyunsaturated fatty acids, PUFA) and coconut oil (low in PUFA). 2. Significantly higher blood pressures developed by 110 d of age in the rats fed on a high-PUFA diet, compared with those fed on the low-PUFA diet. 3. In thymocytes, ouabain-sensitive efflux rate constants were significantly lower in the group fed on the high-PUFA diet. Ouabain-insensitive efflux rate constants were unaffected by diet.
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PMID:The effect of dietary polyunsaturated fat on cation transport and hypertension in the rat. 367 33

The role of circulating humoral agents in the pathogenesis of abnormal vascular wall cation composition in benign and malignant renal hypertension was investigated. Male F344 rats with chronic benign (n = 38) and malignant (n = 44) one-kidney, one clip (1K1C) hypertension and normotensive control rats (n = 63) were studied. Malignant hypertension developed spontaneously and was characterized by failure to thrive, weight loss, oedema, renal insufficiency, anaemia or haemoconcentration and hyperkalaemia. For bio-assay, monolayers of quiescent vascular smooth muscle cells from F344 rats were incubated in plasma or plasma extracts of normotensive and hypertensive rats for measurement of labelled rubidium (86Rb) uptake in the presence and absence of 2 mmol/l ouabain and/or 1 mmol/l furosemide. Compared with controls, ouabain-sensitive Rb uptake of cells was reduced in plasma extracts but not in whole plasma of rats with benign hypertension. Ouabain-sensitive Rb uptake was unchanged and ouabain-insensitive Rb uptake was reduced in both plasma and plasma extracts of rats with malignant hypertension. The latter was due to a reduction in furosemide-sensitive Rb uptake. In malignant hypertension, the increased sodium (Na) content of the aorta which characterizes benign hypertension was reversed and bladder wall Na content was reduced. The findings suggest that in malignant hypertension a circulating, furosemide-like inhibitor of ouabain-insensitive cation transport is the cause of vascular wall Na depletion and of diuresis and natriuresis that trigger the syndrome.
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PMID:Different cation transport inhibitor in benign and malignant experimental renal hypertension. 379 32

In this study erythrocyte phosphate release depended on the intracellular hydrolysis of organic phosphate esters. Total phosphate release was increased in essential hypertension, which suggests an elevated phosphate ester metabolism. Ouabain-sensitive phosphate release was decreased, and the ratio of intracellular Na+/K+ concentrations was increased, a finding consistent with a diminished Na-K-ATPase activity. Furosemide in a concentration of 1.0 mmol/L inhibited erythrocyte phosphate release by half, probably owing to nonspecific membrane effects. The combination of ouabain and furosemide reduced phosphate transfer to a higher degree than did each substance individually. Because of the nonspecific alteration of erythrocyte membrane permeability by furosemide in a concentration of 1.0 mmol/L, ouabain-insensitive, furosemide-sensitive phosphate release and ouabain-insensitive, furosemide-sensitive Na+ efflux (Na-K cotransport) must not be regarded uncritically as specific transport systems.
Hypertension
PMID:Erythrocyte phosphate release in essential hypertension. 399 26

Ouabain-insensitive lithium efflux from lithium-loaded pig erythrocytes has sodium-dependent and sodium-independent components. Lithium effluxes into sodium (total efflux) and sodium-free (leak) media, sodium-dependent lithium efflux, defined as the difference between total and leak fluxes, and changes in red cell cation and water contents as well as blood pressure were assessed serially for 3 weeks in pigs implanted with Silastic strips impregnated with deoxycorticosterone acetate or with Silastic alone and maintained on a high salt diet (200 mEq/day). Significant differences developed between the groups in blood pressure, red cell sodium content, red cell water content, leak flux, and sodium-dependent lithium efflux (maximal difference: 648 +/- 60 vs 256 +/- 81 mumoles of lithium per liter of cells per hour, deoxycorticosterone acetate vs controls; p less than 0.01). Increased sodium-dependent lithium efflux paralleled a decrease of the diffusional leak component of lithium efflux; total lithium efflux was unchanged. Deoxycorticosterone acetate hypertension in pigs is a useful model in which to study factors modulating erythrocyte cation content and lithium transport in vivo. Changes in lithium transport characterized in red blood cells in this form of experimental hypertension may reflect generalized membrane phenomena.
Hypertension
PMID:Erythrocyte lithium transport changes induced by deoxycorticosterone acetate treatment in pigs. 400 90

The functional significance of the Na+,K+-ATPase activity in defining the sensitivity of vascular smooth muscle response to pressor stimuli was studied in guinea pig aortic strips. Subthreshold doses of ouabain (10(-8), 10(-7), 10(-6)M), potentiated the norepinephrine- and angiotensin II-induced contractile responses, dose-dependently. Furthermore, in the presence of subthreshold dose of ouabain (10(-6)M), tension developments were observed with subthreshold doses of norepinephrine and angiotensin II. The mechanism by which subthreshold dose of ouabain potentiated the norepinephrine-induced contractile response was revealed to involve the enhancement both of sensitivity and contractile activity. Ouabain (10(-6)M) potentiated the norepinephrine- and A23187-induced contractile responses, even in the presence of verapamil. These facts indicate that suppression of the vascular Na+,K+-ATPase activity could favor the development of hypertension through potentiating contractile responses to various stimuli and that the potentiation could be a reflection, at least partly, of the decrease in Ca2+-efflux.
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PMID:Na+,K+-ATPase activity and responsiveness of vascular smooth muscle to norepinephrine, angiotensin II and calcium ionophore A23187 in guinea pig aortic strips. 608 30

Ouabain-resistant Na and Li effluxes in erythrocytes from 18 normal subjects and 19 hypertensive subjects were studied in fresh cells that contained about 9 mmol Li and 2.5 or 6.5 mmol Na per liter of erythrocytes after intact cells had been incubated for 5 hours in 110 mM Li, 40 mM Na medium, with or without ouabain 10(-4) M. Outward Na cotransport was estimated at both internal Na concentrations as the furosemide-sensitive unidirectional 22Na efflux from erythrocytes into a Na free-medium containing 75 mM MgCl2. The changes in furosemide-sensitive outward Na transport between the two levels of internal Na were considered as a measure of the response of Na cotransport to the changes in internal Na within its physiological range. At both levels of internal Na, outward Na cotransport was reduced in the majority but not in all of the patients with essential hypertension (p less than 0.05 at 2.5 mmol; p less than 0.001 at 6.5 mmol). The ratio of the changes in Na cotransport to those in internal Na was lower in the hypertensive patients than in the control subjects (17.2 mumol/liter red blood cells/hr/1 mmol in internal Na increase vs 42.2, p less than 0.001). The Li-Na countertransport was increased in a few patients with essential hypertension, with no relationship to cotransport. We conclude that, in essential hypertension, the outward Na + K cotransport is impaired in fresh erythrocytes not treated with PCMBS (2,5 p-chloromercuribenzene sulfonate) or nystatin, even when internal Na is around its physiological range.
Hypertension
PMID:Low sodium cotransport in red cells with physiological internal sodium concentration in essential hypertension. 609 41

Inhibition of the activity of semipurified renal Na+, K+-ATPase and of 3H-Ouabain binding to erythrocytes was used to titrate the level of a plasmatic endogenous inhibitor of the Na+, K+-pump. The inhibition effect of plasma extracts was specific and unrelated to vanadate, calcium and products of proteolysis. Similar results were obtained with the two procedures. An endogenous pump inhibitor could be detected in 28 plasmas of the 42 normotensives investigated so far. In 18 out of 21 normotensives born of hypertensive parent(s) the level was found to be higher than that observed in normotensive controls devoid of hypertensive heredity. 13 untreated essential hypertensives out of 21 also exhibited higher levels of the sodium-potassium pump inhibitor. Plasma levels of the inhibitor appear stable during several months in male subjects. No clear relationship could be established either in normotensives or hypertensives between the pump inhibitor level, the urinary output of Na+, and blood pressure. Neither could any relationship be established between the inhibitor and the intraerythrocytic Na+ concentration. The accuracy of the methodology allows a large scale clinical investigation. It can also be used in the purification of the substance, and preliminary results precised that its molecular weight was inferior to 1 000 daltons and that it was anionic. Purified fractions were obtained after gel filtration, ion exchange chromatography, and high pressure liquid chromatography. Preliminary results suggest that the purified fraction may interfere with the mechanisms of hypertension. They inhibited the Na+-dependent serotonin uptake by human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical and biochemical approach of a circulating Na+-pump inhibitor. 615 34


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