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)

Recent studies suggest that sodium-dependent low-renin hypertension in animals results at least in part from sodium-potassium pump inhibition in blood vessels and heart by a humoral agent released from or influenced by the anteroventral third ventricular area of the brain. For example, a high salt intake in a rat with reduced renal mass results in the appearance of a heat-stable sodium pump inhibitor in the plasma, decreased cardiac Na+, K+-ATPase activity, decreased arterial sodium-potassium pump activity, and hypertension. These changes are reversed by reducing the salt intake or by producing a lesion in the anteroventral third ventricular area of the brain. The course of the development of pump inhibition is similar to the course of the development of hypertension. Sodium-potassium pump inhibition by a humoral agent may also occur in humans with low-renin hypertension. A high potassium intake may stimulate pump activity.
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PMID:Sodium-potassium pump in low-renin hypertension. 630 76

Following the demonstration of a circulating inhibitor of Na+-K+-ATPase in the rat, dog and man, there is now accumulating evidence that the concentration of this inhibitor is increased in patients with essential hypertension:--1. the defect in white cell sodium transport is inversely related to levels of plasma renin activity on a low sodium diet; 2. incubation of leucocytes from normotensive subjects in serum obtained from patients with essential hypertension impairs their ouabain sensitive sodium leucocyte efflux rate constant to the same extent as that found in the leucocytes of hypertensive patients; 3. using a cytochemical technique to measure G6PD activity as a marker of the plasma's ability to inhibit Na+-K+-ATPase it has been found that patients with essential hypertension appear to have an increased concentration of a circulating inhibitor of Na+-K+-ATPase.
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PMID:The relation of the natriuretic hormone to essential hypertension. 631 May 38

It has been shown previously that both low (less than 2 mM) and high (greater than 45 mM) concentrations of extracellular K inhibit the renin secretory rate of rat kidney slices, and that nonidentical Ca-dependent mechanisms appear to be involved. As Rb can substitute for K in many biological systems, the present experiments were designed to compare the effects of K and Rb on renin secretion of rat kidney slices. Adding either KCl or RbCl to a nominally K-free incubation medium stimulated renin secretory rate in concentration-dependent manners; secretory rate was half-maximally stimulated at approximately 1.5 mM and maximally stimulated at approximately 2-3 mM concentrations of either KCl or RbCl. Ouabain completely abolished the basal secretory rate, in either KCl- or RbCl-containing media. These results suggest that the effects of increasing KCl or RbCl in the range of 0.5-4 mM are attributable to stimulatory effects of Rb and K on Na-K-ATPase activity. Renin secretory rate was greatly inhibited by incubating kidney slices in media containing 60 mM concentrations of either KCl or RbCl. A concentration of methoxy-verapamil which completely blocked the inhibitory effects of 60 mM KCl or of 60 mM RbCl failed to antagonize the inhibitory effects of a nominally K-free medium or of media containing ouabain and either 4 mM KCl or 4 mM RbCl. Taken together with previous results, these observations suggest that Rb can substitute for K in the renin secretory process. Furthermore, they support the hypothesis that inhibitors of Na-K-ATPase, and depolarization inhibit renin secretion by Ca-dependent mechanisms which are not identical.
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PMID:Comparison of the effects of rubidium and potassium on renin secretion from rat kidney slices. 633 46

We have recently concentrated our efforts on bioassay of plasma supernatant from animals with experimental low-renin hypertension (one-kidney, one-wrapped in dogs, and one-kidney, one-clip, and reduced renal mass in rats) for sodium-potassium pump inhibiting activity. We have observed changes compatible with inhibitory activity by using three different in vitro bioassays: 1) ouabain-sensitive 86Rb uptake by the normal rat tail artery, 2) short-circuit current in the toad bladder, and 3) membrane potential in the rat tail artery. We have also generated evidence suggesting that the humoral pump inhibitor(s) comes from or is influenced by the anteroventral third ventricle area of the brain and that it acts on the vascular smooth muscle cell at least in part by depolarizing the membrane. These findings are compatible with our 1976 hypothesis in which we proposed that in volume-expanded hypertension there is a circulating agent that suppresses cardiovascular membrane Na+,K+-ATPase, which results in reduced activity of the Na+-K+ pump and hence increased contractility of heart, arteries, and veins and that in blood vessels the increased contractility may be secondary to depolarization. We attempt to relate these findings to those in the literature on monovalent ion transport in blood cells of hypertensive subjects.
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PMID:The role of a humoral sodium-potassium pump inhibitor in low-renin hypertension. 634 2

Periventricular forebrain regions participate in body fluid and cardiovascular regulatory mechanisms that are intimately related to neural participation in experimental hypertension. Ablation of preoptic-hypothalamic periventricular tissue surrounding the anteroventral third ventricle (AV3V) disrupts both angiotensin (AngII) and sodium regulatory mechanisms and prevents experimental hypertension in either renin-dependent or -independent models. When AV3V is spared, and central AngII pressor mechanisms are interrupted by subfornical organ ablation or anterior hypothalamic knife cuts, renin-dependent but not renin-independent models of hypertension are prevented. Volume-expanded models of hypertension may be mediated by a natriuretic hormone that also inhibits the sodium-potassium pump in vascular smooth muscle, resulting in increased vasoconstriction. Volume expansion-induced release of this humoral ATPase inhibitor is attenuated in rats with AV3V lesions. In the renin-independent, reduced renal mass model, development of hypertension is correlated with increased plasma levels of sodium-potassium pump inhibitor. AV3V ablation blocks both the hypertension and the increase in humoral ATPase inhibitor. Thus, Thus, central angiotensin pressor and natriuretic mechanisms overlap in AV3V, and prevention of renin-dependent and volume-dependent models of experimental hypertension by AV3V ablation appears linked to disruption of these functionally separable systems.
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PMID:Periventricular forebrain mechanisms for blood pressure regulation. 636 Jul 15

The effects on in vitro renin release from rat kidney cortex of various agents which are thought to alter intracellular Ca were investigated. Incubation in Ca-free medium had no effect on basal or isoprenaline-stimulated renin release, but the addition of EDTA stimulated renin release. Angiotensin II (ANG II) and ouabain both inhibited basal and isoprenaline-stimulated renin release, and external Ca was important in this effect. Verapamil reduced the fall in basal renin release and the inhibitory effect of ANG II. In addition, verapamil blocked the inhibition by ANG II, but not by ouabain, of isoprenaline-stimulated renin release. Isoprenaline may stimulate the Na,K-ATPase leading to increased Ca efflux via Na-Ca exchange, whereas ouabain may have the opposite effect. ANG II probably stimulates Ca influx and release from intracellular stores.
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PMID:The role of calcium in the control of renin release. 644 9

Plasma renin activity (PRA, ng AI/ml/hr), plasma aldosterone (PA, ng%) and renal Na+-K+-ATPase (micron m PO 4/mg protein/hr) were measured in tow groups of eight spontaneously hypertensive rats (SHR), two groups of eight Dahl salt hypertensive rats (SS), and their controls (16 normal Wistar and 16 salt-resistant rats). Measurements were made in one group after 2 weeks on a normal (0.48% sodium) and in the other group after 2 weeks on a low (0.01% sodium) sodium diet. After a normal sodium diet, PRA and PA were lower in both groups of hypertensive rats than in control normotensive animals. Renal NA+-K+-ATPase was lower in SS than in controls: in SHR it was not different from control. On a sodium-free diet, SHR exhibited a rise in renal Na+-K+-ATPase but PRA and PA remained low. In contrast, under similar conditions PRA, PA, and renal Na+-K-ATPase increased in SS rats, although to a lesser extent than in SR. These results suggest that under basal conditions and after low salt diet, renal Na+-K+-ATPase activity in SHR behaves as it does in normal rats. However, the changes are independent of PA in SHR. The reduction in PRA and PA in SS suggest volume expansion hypertension. IN SHR, volume expansion is not present, and renal Na+-K+-ATPase is not altered. Enzyme activity is lower in SS than in SHR and control. This suggests that some factor that results from volume expansion may be responsible for inhibition of renal Na+-K+-ATPase.
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PMID:Renal Na+-K+-ATPase in Okamoto and Dahl hypertensive rats. 645

It has been suggested that circulating natriuretic hormone may be important in the pathogenesis of essential hypertension by inhibiting the ouabain-sensitive Na+, K+-ATPase pump and that this effect should be more pronounced in low-renin hypertensives. We have studied serum and red blood cell sodium and potassium concentrations in vitro, before and after exogenous ouabain, in White normotensives and Black subjects with essential hypertension and in two groups of renal patients. No convincing evidence of sodium or potassium inhibition could be found in Blacks with either low-renin or high-renin hypertension. Striking inhibition was seen in the renal groups, supporting a circulating natriuretic factor, but there were anomalies within the renal groups, which suggest additional cell membrane abnormalities.
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PMID:Does the natriuretic hormone play a role in hypertension in South African blacks? 648 63

1. Renin secretion of rat renal cortical slices was measured as a function of extracellular K and ouabain concentrations in the incubation medium.2. A sigmoid relationship was found between renin secretion and log K concentration over the range 1.0-4.0 mM. Secretion was maximal at about 2.25 mM-K and half-maximal at about 1.43 mM-K.3. In media containing 4.0 mM-K, ouabain at 10(-8), 10(-7), and 10(-6)M did not affect renin secretion. Higher concentrations of ouabain inhibited secretion. A sigmoid relationship was found between% inhibition of secretion and log ouabain concentration (10(-6)-10(-3)M). Inhibition was half-maximal at 2.3 x 10(-5)M and complete at 10(-3)M-ouabain.4. Lowering extracellular K concentration from 4.0 to 2.25 mM shifted the dose-effect curve of ouabain to the left. At 2.25 mM-K, inhibition of renin secretion was half-maximal at 10(-5)M-ouabain.5. The inhibitory effect of 2 x 10(-5)M-ouabain (twice the dose for 50% inhibition) in media containing 2.25 mM-K was nearly identical to the combined effect of lowering K to 1.43 mM (the concentration required for 50% inhibition) and adding 10(-5)M-ouabain. This observation suggests that ouabain and low extracellular K act at a common site, presumably on Na, K-ATPase activity, to inhibit renin secretion.6. Neither 10(-3)M-ouabain nor K-free medium inhibited renin secretion when the concentration of free Ca in the medium was lowered to < 10(-8)M. Therefore it is proposed that as a result of Na, K-ATPase inhibition, (a) intracellular Na increases, (b) intracellular Ca increases via Na-Ca exchange, provided that extracellular Ca exceeds 10(-8)M, and that (c) Ca accumulation, in some unknown manner, inhibits renin secretion from rat renal cortical slices.
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PMID:Separate and combined effects of ouabain and extracellular potassium on renin secretion from rat renal cortical slices. 699 69

Renin release was measured in the isolated rat kidney perfused with a recirculating artificial medium containing bovine serum albumin at 6.7 g per 100 ml of 11 g per 100 ml. At the higher concentration of albumin, glomerular filtration ceased and the rate of renin release over 70 minutes of perfusion was increased 6-fold. The addition of ouabain to the perfusate containing 11 g per 100 ml inhibited the release of renin, suggesting that inhibition of Na-K-ATPase or the related changes in cellular volume or composition prevented renin release. Lowering the osmolality of the perfusate by reducing the concentration of sodium chloride also prevented the increase in renin secretion produced by perfusion with 11 g per 100 ml albumin. Increasing the osmolality of the perfusate with mannitol restored the augmented renin release. These results are consistent with the hypothesis that alterations in the volume of certain cells, perhaps in the juxtaglomerular apparatus itself, can control renin release.
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PMID:Stimulation of renin release by hyperoncotic perfusion of the isolated rat kidney. 703 19


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