Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Red cell membrane Na(+)-K+ transport systems, renin-angiotensin-aldosterone system (RAAS) and atrial natriuretic factor (ANF) were studied in a group of 50 mild essential hypertensive patients (n = 25 for each group) age, sex and blood pressure matched. Na(+)-K+ ATPase and intracellular Na+ (Na+ i) were significantly different between the two groups (p less than 0.01). A slight difference was also seen for the Na(+)-K+ cotransport (p less than 0.05) as a likely consequence of the differences in the methodology of Na+ charge to study its efflux from the red cells in vitro. A negative correlation (r = -0.47, p less than 0.01) was observed between ANF and Na(+)-K+ cotransport suggesting an interrelationship of the two systems in the homeostasis in body fluid and electrolytes.
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PMID:[Erythrocyte cation transport in arterial hypertension: interrelation with the renin-angiotensin-aldosterone system and the atrial natriuretic factor]. 256 Sep 22

Concentrations of sodium-transport inhibitors (STI) which block the sodium-potassium-ATPase pump are increased in the plasma and urine of volume-expanded and low-renin hypertensive humans and animals. To evaluate the physiologic relevance of STI to blood-pressure-raising mechanisms, we have examined the in vitro properties of STI extracted from the urine of human subjects. STI produced a significant (by ANOVA: P less than .01) dose-contraction response in the isolated rabbit femoral artery. Moreover, small noncontractile doses of STI in this in vitro preparation produced a fivefold leftward shift in the contraction dose-response curve of norepinephrine (P less than .01) and a threefold shift for angiotensin II (P less than .01); at lower, physiologic, concentrations of these vasoconstrictor hormones the amplifications in contraction caused by STI ranged from 100% to 500%. In studies in calcium-free tissue bath solutions, the direct contractile action of STI was abolished; however, its amplification of responses to norepinephrine remained, suggesting that this latter effect of STI is not entirely dependent upon calcium influx into vascular smooth muscle cells. The glycoside ouabain produced effects identical to those of STI in arteries, but its actions on a rabbit atrium preparation were different: ouabain stimulated powerful inotropic effects, whereas human STI failed to cause myocardial contractions even though the amounts of STI administered had the same sodium-transport inhibitory capacity as the ouabain. Thus, the actions of human STI are primarily in the peripheral circulation, where they directly produce arterial contractions and also enhance contractile responses to other pressor hormones, suggesting that they may have a role in regulating systemic blood pressure.
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PMID:Effects of a human-derived sodium transport inhibitor on in vitro vascular reactivity. 280 70

Normal-renin essential mesor hypertensives are characterized by a consistent increase in erythrocyte membrane-bound Na/K-ATPase activity. Low-renin essential hypertensives exhibit, in contrast, a lower activity in Na/K-ATPase of cell membranes. This study documents a third disorder characterized by a temporal shift in the rhythmic activity of the erythrocyte membrane-bound Na/K-ATPase in normal-renin hypertensives. The disorder causes the synchronism with the aldosterone circadian rhythm to be invariably lost. The uncoupling phenomenon could be invoked to explain the inversion in the day-night sodium excretion rate found in essential hypertensives. In addition, it suggests that the circadian rhythm in Na/K-ATPase is under the control of cycling factors other than aldosterone.
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PMID:Internal desynchronization between circadian rhythms of plasma aldosterone and erythrocyte membrane-bound Na/K-ATPase. 281 94

We tested the hypothesis that a metabolic error may be the triggering mechanism which leads to blood-vessel hypertrophy and hypertension. Young spontaneously hypertensive rats (SHR) were fed a moderately high salt diet to exacerbate the purported metabolic error. Haematocrit values and rubidium transport were measured as evidence of renal ATP deficiency and blood-vessel adaptation. The renin system was inhibited in two groups of SHR by giving them enalapril to determine whether angiotensin II was involved in blood-vessel adaptation. Spontaneously hypertensive rats fed the moderately high salt diet had higher haematocrit values than normotensive rats fed the same diet or SHR fed Purina rat food, suggesting a renal ATP deficiency. Spontaneously hypertensive rats had higher Na+,K+-ATPase activity in thoracic aorta after 60 min incubation than a similar group given enalapril (P less than 0.001), suggesting blood-vessel adaptation. Possibly, angiotensin II within the vasa vasorum stimulates hypertrophy which, according to the Folkow hypothesis, leads to higher blood pressure, but may concomitantly increase the respiratory chain units which provide ATP for renal function and ion transport.
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PMID:Effect of a renin-system inhibitor on blood-vessel adaptation in spontaneously hypertensive rats. 282 Dec 7

In hypertension, mainly low renin subjects, a plasma Na-K ATPase inhibitor has yet been demonstrated. Moreover, it has been established that the concentration of this activity may be modulated by variations of the sodium and water balance. In the present study, such an activity and its role has been searched in the plasma of young healthy normotensive population. Its potential natriuretic property has also been tested. Twenty male subjects, younger than 30, volunteered 3 very different sodium diets: normal (+/- 170 mM/d), very low (-20 mM/d) and very high sodium intake (+340 mM/d). At the end of each period, some clinical and biological parameters have been studied: blood pressure, weight, vascular resistances and reactivity to norepinephrine, 24 h natriuresis, and plasma renin activity. Furthermore, the plasma natriuretic activity has been tested after filtration of the plasma across different Amicon filters to measure the effect of plasma extracts from 500 to 10,000 daltons (LMW) on fractional sodium excretion (FENa) after injection of such extracts in vivo in rat renal artery. For detection of a plasma Na-K ATPase inhibitor activity, 1/5 th diluted fresh plasma and LMW extracts have been incubated with purified rabbit renal Na-K ATPase enzyme and compared with the activity of this enzyme without such an incubation of plasma. We have observed that when the amount of sodium in the diet is higher, weight, systolic blood pressure, and vascular reactivity to norepinephrine increase. In the same condition, there are greater natriuretic activity in the LMW extracts and Na-K ATPase inhibitor activity in fresh plasma and LMW extracts of the normotensive people.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Presence and regulation of plasma with natriuretic and Na-K ATPase inhibitory properties in normotensive subjects]. 282 49

Plasma and urine levels of an endogenous digitalis-like compound (EDLC) are increased in low renin Na+-dependent experimental hypertension, in some normotensive offspring of hypertensive patients and in some essential hypertensive patients. Urine-drived EDLC was purified from 550 L of urine from essential hypertensive patients (n = 8) and from normotensive subjects with a family history of hypertension (n = 27), using flash chromatography on C18 reversed-phase, anion exchange chromatography and various reversed-phase high performance liquid chromatographies. The mechanism of Na+-K+ ATPase inhibition and the related effects of semipurified urine-derived EDLC were studied and compared with those of ouabain. Its action was similar to that of ouabain in 8 out of 10 of the tests applied. The main effects of such a compound were the depression of Na+-K+ pump activity of human erythrocytes, the inhibition of 5-hydroxytryptamine reuptake by human platelets, and the induction of natriuresis in urethanized rats. Therefore, EDLC may be considered as one of the natriuretic hormones whose mechanism of action closely resembles that of ouabain.
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PMID:An endogenous digitalis-like compound extracted from human urine: biochemical and chemical studies. 282 38

A local increase in extracellular potassium concentration [K+]o, up to about 8 mEq/liter, by topical application or intra-arterial infusion of iso-osmotic solutions of K+ salts, causes arteriolar dilation and decreased resistance to blood flow in systemic vascular beds. A local decrease in [K+]o over physiologic ranges induces arteriolar constriction and increased resistance to blood flow. K+ vasodilation is accompanied by hyperpolarization of the smooth muscle cell, whereas the vasoconstriction is accompanied by depolarization. All of these responses can be blocked by ouabain, a potent Na+,K+-ATPase inhibitor. Thus it is thought that K+ vasodilation results from stimulation of the electrogenic Na+-K+ pump, and that the constriction results from its inhibition. Acute generalized inhibition of the Na+,K+-ATPase and Na+-K+ pump (hypokalemia, strophanthidin, methylguanidine, vanadate) in the anesthetized dog can raise blood pressure. In experiments in animals, myocardial Na+,K+-ATPase and vascular Na+-K+ pump activities were decreased in low-renin hypertension, and vascular Na+-K+ pump activity was decreased following acute volume expansion, changes associated with bioassay evidence of a Na+-K+ pump inhibitor in the plasma. The inhibitor appears to arise in, or to be influenced by the area of the anteroventral third ventricle of the brain. It induces electrogenic depolarization of vascular smooth muscle cells and may inhibit norepinephrine uptake by adrenergic nerve terminals. Potassium and a circulating endogenous Na+,K+-ATPase inhibitor of unknown molecular structure may partly regulate the mechanical activity of cardiovascular muscle and participate in the genesis of certain forms of hypertension. Potassium may be of value in the prevention and therapy of hypertension, partly by virtue of its vasodilator activity.
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PMID:Potassium, Na+-K+ pump inhibitor and low-renin hypertension. 283 Oct 2

Changes in plasma levels of Na+, K+-ATPase inhibitors with salt loading were studied in eight patients with essential hypertension. By improving the assay method of Na+, K+-ATPase inhibitors to distinguish ouabain and vanadate, two types of inhibitors were detected in the plasma of patients with essential hypertension: One was ouabainlike and the other was nonouabainlike. The ouabainlike inhibitor was detected at low KCl concentrations (0.1 mM) in the assay buffer, and the nonouabainlike inhibitor was detected at a high KCl concentration (10 mM). By increasing dietary sodium chloride from 2 g/day for 5 days to 20 g/day for 6 days, systolic blood pressure increased significantly from 122 +/- 3.9 to 138 +/- 3.8 mmHg (p less than 0.005), whereas plasma renin activity decreased significantly from 3.9 +/- 0.8 to 0.8 +/- 0.3 ng/ml/hr (p less than 0.002). Under these conditions, the ouabainlike inhibitor increased significantly from 6.2 +/- 3.9% to 30.5 +/- 5.9% inhibition (p less than 0.005), after increasing dietary sodium. Furthermore, plasma level of the ouabainlike inhibitor correlated significantly with both systolic blood pressure (p less than 0.05) and daily urinary sodium excretion (p less than 0.01). In contrast, the plasma nonouabainlike inhibitor did not change with high sodium intake and did not correlate with blood pressure and daily urinary sodium excretion. These findings suggest that a ouabainlike inhibitor is involved in the maintenance of high blood pressure induced by high sodium intake in patients with essential hypertension. The role of the nonouabainlike inhibitor in blood pressure regulation is still unknown.
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PMID:Increase in plasma ouabainlike inhibitor of Na+, K+-ATPase with high sodium intake in patients with essential hypertension. 283 25

Since angiotensin (ang) II blockers attenuate the centrally-induced pressor responses to a Na+, K+-ATPase inhibitor, ouabain, a brain renin-ang system is assumed to be involved in this pressor mechanism. Centrally-induced pressor responses to hypertonic saline were also blocked with ang II blockers. Thereby, the increase in the plasma level of digoxin-like immunoreactivity was abolished with simultaneous infusions of an ang II analogue or atrial natriuretic polypeptide (ANP). These results indicate that the pressor responses to sodium salts are mediated via inhibition of the brain Na+, K+-ATPase, and that the brain renin-ang system is involved in this mechanism. We noted the existence of a digoxin-like immunoreactive substance (DLI) containing neurons in the hypothalamus (PVN, SON) with the fibers densely distributed in the AV3V area including OVLT, SFO and the median eminence, an area where receptors for ang II are also distributed (1,2). Since pressor responses to intracerebroventricular (ICV) infusions of hypertonic NaCl are abolished with ICV pretreatment with ang II blockers, a brain renin-ang system may be involved in this mechanism. We then searched for a possible relationship between the central effects of NaCl, a brain renin-ang system and an endogenous Na+, K+-ATPase inhibitor in the hypothalamus.
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PMID:Brain renin-angiotensin system and the hypothalamic, digitalis-like Na+, K+-ATPase inhibitor in rats. 285 80

The relationship between changes in the pressor response to infused noradrenaline induced by intravenous injection of ouabain, an Na+,K+-ATPase inhibitor, and plasma renin activity and plasma ionized calcium was examined in 16 normotensive subjects and in 16 patients with essential hypertension. These patients were divided into 11 normal-renin and five low-renin essential hypertensives. The pressor response was significantly greater in low-renin hypertensives than in normotensives and normal-renin hypertensives. Following the injection of ouabain, the pressor response was significantly increased with no change in basal levels of blood pressure, plasma noradrenaline concentration, plasma calcium and plasma parathyroid hormone in both normotensives and essential hypertensives. The pressor response to noradrenaline was negatively correlated with levels of plasma noradrenaline and calcium after the injection of ouabain as well as before the injection in normotensives and essential hypertensives. The regression line between the pressor response and that of plasma noradrenaline or plasma calcium was significantly shifted towards a higher pressor response in normotensives, but not in essential hypertensives. The changes in the pressor response to noradrenaline induced by the injection of ouabain was significantly smaller in essential hypertensives, particularly in low-renin hypertensives, compared with normotensives. These results suggest that: (1) ouabain increases the pressor response to noradrenaline; (2) this increase is related to calcium metabolism; (3) endogenous Na+,K+-ATPase inhibitor(s) might be elevated in essential hypertensives; and (4) an increase in endogenous Na+,K+-ATPase inhibitor might, therefore contribute to an enhanced noradrenaline response in essential hypertensives, particularly in low-renin hypertensives.
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PMID:The effect of ouabain on pressor responses to infused noradrenaline in patients with essential hypertension. 285 44


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