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)

We have previously shown that Na+-K+ pump activity (ouabain-sensitive 86Rb uptake) is decreased in vascular tissue of animals with various forms of low renin hypertension. In the present study we measured Na+-K+-ATPase activity, the energy source for Na+-K+ pumping, in membrane fractions prepared from myocardial tissue of rats with chronic one-kidney, one-clip hypertension and their one-kidney normotensive controls. Membranes were prepared by two independent methods: microsomal fractions (method 1) and fractions prepared by the hypotonic LiBr method of Dhalla et al. (method 2). In membranes prepared from left ventricles of the hypertensive rats (by method 1) Na+-K+-ATPase activity was decreased, Mg2+-ATPase activity was increased, and the sialic acid content and 5'-nucleotidase activity (two putative membrane markers) were unchanged relative to the control rats. The sensitivity of cardiac Na+-K+-ATPase to inhibition by ouabain was also unchanged. Na+-K+-ATPase activity was also decreased in the right ventricles (method 1) of these hypertensive rats, suggesting that this defect is probably not pressure related. In membranes prepared from the left ventricles of the hypertensive rats by method 2, Na+-K+-ATPase activity was again reduced, whereas the Mg2+-ATPase and 5'-nucleotidase activities were unchanged relative to the controls. These studies suggest that myocardial Na+-K+-ATPase activity is suppressed in rats with this low renin form of hypertension and the possible effect of this suppression on myocardial contractile activity is discussed.
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PMID:Decreased myocardial Na+-K+-ATPase activity in one-kidney, one-clip hypertensive rats. 613 90

The effect of intrarenal infusion of ouabain (90 micrograms/kg) on renin release was examined in the anaesthetized dog. Ouabain reduced cortical Na-K-ATPase activity to 23% and outer medullary activity to 18% of the control level. During renal arterial constriction to a perfusion pressure below the autoregulatory range, renin release rose from 1.2 +/- 0.4 to 47.4 +/- 6.9 micrograms/min (P less than 0.001). This response was abolished by ouabain. When superimposed on renal arterial constriction, beta-adrenergic stimulation enhanced renin release from 25.6 +/- 10.7 to 56.9 +/- 9.5 micrograms/min (P = 0.02) at a urinary sodium excretion of 2 +/- 1 mumol/min. After ouabain, the corresponding increment substantially decreased since release rose from 5.6 +/- 2.0 to 19.9 +/- 5.3 micrograms/min only (P = 0.02), at a urinary sodium excretion of 140 +/- 67 mumol/min. When glomerular filtration was reduced to zero by ureteral occlusion in one series, renin release increased to 22.6 +/- 5.1 but was reduced (P less than 0.05) by ouabain to 13.5 +/- 5.5 micrograms/min and superimposed isoproterenol had no effect. According to these observations, ouabain inhibits renin release by a direct effect on the afferent arteriole through constriction of the autoregulating renin-secreting segment.
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PMID:Ouabain inhibits renin release by a direct renal haemodynamic effect. 614 85

The presence in plasma extracts of a sodium pump inhibitor with digitalis-like properties was investigated by two complementary tests: decrease in the affinity of ouabain binding to human red blood cells and inhibition of Na+,K+-ATPase. The results of the two methods were correlated (r = 0.76, n = 44, p less than 0.01), suggesting that the same factor may be responsible for both effects. All subjects with elevated values were hypertensive or normotensive and had a family history of hypertension. Forty percent of the subjects in these two groups had high inhibition values. The elevation was significant (p less than 0.01) when compared with values in normotensive subjects with no hypertensive heredity. Increased inhibition was observed in patients taking beta-blocking agents; conversely, diuretics normalized the values. No correlation was found between pump inhibition and age, sex, blood pressure, levels of plasma K+ or Na+, or plasma renin activity. These data show the existence of a sodium pump inhibitor in the plasma of some subjects and point to a possible association with hypertension. They also underline the importance of genetic background and the heterogeneity of essential hypertension.
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PMID:Plasma sodium pump inhibitor in essential hypertension and normotensive subjects with hypertensive heredity. 620 59

In this review, we first present chronologically our evidence suggesting that a circulating Na+,K+-ATPase and Na+-K+ pump inhibitor in part regulates the mechanical activity of the muscle in the cardiovascular system. We then present the relevant findings from other laboratories. The evidence from our laboratories includes the observations that local hyperkalemia decreases small-vessel resistance and local hypokalemia increases small-vessel resistance and that these responses can be blocked by ouabain, a potent Na+,K+-ATPase inhibitor. Myocardial Na+,K+-ATPase and vascular Na+-K+ pump activities are decreased in animals with experimental low-renin hypertension, vascular Na+-K+ pump activity is decreased in animals following acute volume expansion, and these changes are associated with bioassay evidence for a Na+-K+ pump inhibitor in the plasma. The inhibitor appears to come from, or be influenced by, the anteroventral third ventricle (AV3V) area of the brain. It produces electrogenic depolarization of the vascular smooth-muscle cell and may inhibit norepinephrine uptake by adrenergic nerve terminals. The evidence from other laboratories includes the observations that there is (a) a pressor and vascular sensitizing agent in the plasma of animals and patients with low-renin hypertension, (b) reduced Na+-K+ pump activity in the leukocytes of some patients with essential hypertension, and (c) a Na+,K+-ATPase and Na+-K+ pump inhibitor in the plasma of some patients with essential hypertension.
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PMID:The role of a humoral Na+,K+-ATPase inhibitor in regulating precapillary vessel tone. 620 53

Expansion of the extracellular fluid volume (ECFV) promotes the release of a small molecular weight (less than or equal to 1,000 Daltons) humoral natriuretic factor. The resulting natriuresis is accompanied by inhibition of renal cortical tissue and red blood cell Na-K-ATPase activity. This transport inhibitor, presumably an acidic peptide derived from a larger precursor molecule, was so far recovered from the serum and urine of rat, dog, and man, and from renal cortical tissue homogenate. Using Sephadex G-25 gel chromatography the inhibitor is eluted in the post-salt fraction IV. Its natriuretic action is demonstrated by bioassay methods, it depresses sodium transport of isolated amphibian membranes and inhibits Na-K-ATPase enzyme activity in vitro. The inhibitor isolated from human urine binds to specific antibodies against digoxin. This natriuretic factor is absent in patients with arterial hypotension and in edematous patients with secondary aldosteronism. In contrast, high inhibitory activity is found in patients with primary aldosteronism, a condition which represents the most classical type of low renin volume-dependent hypertension. Since enzyme inhibition by this humoral endogenous agent probably extends to various Na-K-ATPase-dependent transport systems including vascular smooth muscle fibers, depression of their Na-K pump will raise intracellular concentrations of sodium and calcium and thereby induce vasoconstriction. It is therefore tempting to speculate that the natriuretic hormone plays an important role in the pathogenesis of volume-dependent arterial hypertension.
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PMID:Natriuretic hormone - a circulating inhibitor of sodium- and potassium-activated adenosine triphosphatase. Its potential role in body fluid and blood pressure regulation. 627 45

A cytochemical technique that measures the ability of plasma to stimulate guinea-pig renal glucose-6-phosphate dehydrogenase (G6PD) activity in vitro, which is a marker of its ability to inhibit Na+-K+-adenosine-triphosphatase (Na+-K+-ATPase), was used in 19 patients with essential hypertension and 23 normotensive, healthy subjects. The ability of plasma to stimulate G6PD was significantly greater in the hypertensive patients when they were taking their normal sodium diet than in the normotensive subjects, and was significantly correlated with blood pressure. The ability of plasma to stimulate G6PD was inversely correlated with plasma renin activity in the hypertensive patients and increased with age and sodium intake in the normotensive subjects. These results support the hypothesis that essential hypertension, and also perhaps the increase in blood pressure with age in communities that consume large quantities of salt, is in part due to an increase in a circulating concentration of an inhibitor of Na+-N+-ATPase.
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PMID:Evidence for a raised concentration of a circulating sodium transport inhibitor in essential hypertension. 627 73

1. The plasma's ability to stimulate guinea-pig renal glucose 6-phosphate dehydrogenase (G6PD) in vitro was measured by a cytochemical technique in 23 normotensive subjects and 19 patients with hypertension, all of whom were studied on their normal sodium intake. The ability of plasma to stimulate renal G6PD was significantly (P less than 0.001) increased in the hypertensive patients (mean 195 +/- 52 units/ml) compared with the normotensive subjects (mean 22.2 +/- 5.8 units/ml). In all 42 individuals, there was a significant correlation between diastolic pressure and the ability of plasma to stimulate G6PD (r = 0.69 P less than 0.001). 2. The ability of plasma to stimulate G6PD was greatest in the hypertensive patients with values of plasma renin activity below the normal range. In the normotensive subjects the ability of plasma to stimulate G6PD was significantly greater in the older subjects. 3. As the ability of plasma to stimulate G6PD reflects its ability to inhibit Na+,K+-dependent ATPase, these results suggest that patients with essential hypertension have an increase in a circulating inhibitor of Na+,K+-ATPase. The results support the hypothesis that a rise in a circulating sodium transport inhibitor may, in part, be responsible for the rise in blood pressure in essential hypertension, and may form the link between salt intake, abnormalities of sodium transport and a rise in blood pressure.
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PMID:An increase in a circulating inhibitor of Na+,K+-dependent ATPase: a possible link between salt intake and the development of essential hypertension. 627 66

Changes in plasma renin activity (PRA) were monitored in six mildly hypertensive men after intravenous doses, in seven separate experiments, of placebo, digoxin, potassium canrenoate, potassium canrenoate with digoxin, furosemide, furosemide with digoxin, and potassium canrenoate with furosemide and digoxin. Potassium canrenoate has been used as a rapid source of canrenone, which has been recently shown to be a competitive antagonist of ouabain at its Na-K-ATPase receptor site. Potassium canrenoate infusion reversed the hyporeninemic effect of digoxin. This result has been taken as evidence that: (1) antialdosteronic drugs can also reverse digoxin effects at extracardiac level and (2) the Na-K-ATPase system is involved in the renin secretory mechanism. A seemingly identical reversal of the hyporeninemic effect of digoxin was induced by furosemide, which, when given alone, stimulated renin secretion. The simultaneous administration of potassium canrenoate, digoxin, and furosemide induced an increase in PRA on the same order as that after furosemide alone. This result indicates that furosemide stimulates renin release by affecting a biochemical system other than that affected by digoxin.
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PMID:Canrenoate reversal of inhibitory effects of digoxin on basal and furosemide-stimulated renin secretion. 628 24

Recent studies suggest that sodium dependent low renin hypertension results in part from the release of a ouabain-like factor, perhaps natriuretic hormone, from the brain. This humoral factor inhibits Na+, K+-ATPase and hence the active pumping of sodium and potassium in the muscle cells of blood vessels and heart. The pump suppression causes increased contractile activity and hence increased arterial blood pressure. In the muscle cells of the blood vessels, the increased contractile activity appears to be related to membrane depolarization.
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PMID:Humoral factors and the sodium-potassium pump in low renin hypertension. 629 71

The effects of ouabain and furosemide on renin secretion, renal function, and renal Na+-K+-ATPase were investigated in anesthetized dogs. Furosemide (2 mg/kg) induced significant diuresis, natriuresis, an increase in renal blood flow (RBF), and a fivefold increase in renin secretory rate (RSR), but no changes in glomerular filtration rate (GFR). Infusion of ouabain (1 microgram . kg-1 . min-1) into one renal artery during furosemide diuresis increased fractional sodium excretion from 22 +/- 2 to 30 +/- 3% from the ipsilateral kidney but did not change urine flow, RBF, or GFR, whereas RSR fell to control values (698 +/- 203 to 137 +/- 43). When ouabain preceded furosemide, the rise in RBF and RSR induced by furosemide was abolished but sodium excretion increased. Ouabain infused in vivo inhibited Na+-K+-ATPase in microsomal fractions from cortex (34%) and medulla (27%) as compared with control. Neither saline nor furosemide exerted any effect on Na+-K+-ATPase. Moreover, the effect of ouabain alone on Na+-K+-ATPase was not different from that of ouabain plus furosemide. No changes in Mg2+-ATPase were detected in any of the experiments. These results indicate that inhibition of renal Na+-K+-ATPase abolishes furosemide-induced renin secretion despite potentiation of the natriuretic effect of the diuretic. It is apparent that the level of activity of Na+-K+-ATPase is of prime importance for renin secretion. In addition, ouabain may act directly on the juxtaglomerular cells to inhibit renin secretion.
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PMID:Renal Na+-K+-ATPase in renin release. 629 14


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