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)

Cortisol, insulin, somatotropin, thyreotropin, thyroxine, triiodothyronine, testosterone, aldosterone, c-AMP, c-GMP, prostaglandins (PGF1-x, PGF2-x, PGA + E), and renin concentrations in serum or plasma of the venous blood of the third international crew of the scientific orbital complex of "Soyuz 29 - Salyut 6 - Soyuz 31" were determined following the 7-day space flight. The increased activity of the renin-angiotensin-aldosterone system before the flight as well as variations in the pressor/depressor prostaglandin ratios indicate an increased strain during the pre-flight period. During the first stage of the post-flight period some parameters were changed due to the landing process and the returning to earth gravity. The associated physical load and the onset of reactions for enhancement of the orthostatic tolerance resulted in an increase of cyclic nucleotid and thyroxine concentrations. The relatively higher levels of the pressor PGs of group F in comparison with the prostaglandins A + E could be evaluated as a compensatory reaction for enhancement of the orthostatic tolerance. The cortisol and STH concentrations increased with growing motor activity. The variations seen after the 7-day space flight were essentially within the reference areas. It may be assumed that the readaptation was not yet totally accomplished by the 8th day after landing.
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PMID:[Results of endocrinolgic studies of the 3rd international crew of the scientific orbital station complex; Soyuz 29 - Salyut 6 - Soyuz 31 (joint space flight enterprise of the USSR - GDR). 2. Hormones and biologically active substances in blood]. 675

Six normotensive volunteers were infused with L-adrenaline at 0.01, 0.03, 0.05, 0.075 and 0.10 microgram/kg-1 min-1, each increment lasted 10 min. Plasma adrenaline rose from 0.27 to 4.61 nmol/l, and there were dose-related increases in plasma renin activity, blood glucose, plasma cyclic AMP and plasma free fatty acids, but not in plasma noradrenaline and cyclic GMP. Levels of circulating adrenaline previously noted in essential hypertensives had minimal cardiovascular effects. The secretion rate of adrenaline and its rate of clearance from the circulation were calculated from plasma samples taken during an hour-long infusion (0.083 +/- 0.006 microgram kg-1 min-1) of L-adrenaline in the same individuals. The secretion rate ranged from 1.40 to 6.01 nmol/min with a mean (+/- SEM, 6) of 2.82 +/- 0.76 nmol/min. Mean clearance (+/- SEM, 6) was 9.41 +/- 1.37 l/min and ranged from 4.86 to 14.61 l/min. The decline of plasma adrenaline following the infusion was biexponential. Plasma adrenaline is unlikely to be of primary importance in the elevation of blood pressure, either directly, via renin release or by noradrenaline release via presynaptic beta receptors. However, variation in clearance between subjects limits the use of plasma levels as an interindividual index of adrenal release of adrenaline. The relationship between sympathoadrenal activity and plasma adrenaline may be further perturbed by equilibration between the circulation and sites of tissue uptake. The lower levels of plasma adrenaline than of noradrenaline appear to result from both a slower rate of secretion and a higher rate of clearance from the circulation.
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PMID:Circulating adrenaline and blood pressure: the metabolic effects and kinetics of infused adrenaline in man. 677 75

To study the effect of kallikrein on renal renin release, we superfused rat renal cortical slices with 3.5 to 140 milliesterase units (mEU)/ml of purified rat urinary kallikrein. Kallikrein was a potent stimulus of renin release. Renin rose in a dose-dependent fashion from 70 mEU/ml to 140 mEU/ml. The response to 140 mEU/ml was greater than that seen with maximal doses of prostaglandin E2 (170 +/- 43%, P < 0.05) and at least the same as isoproterenol (242 +/- 49% increase), or dibutyryl cyclic AMP (272 +/- 40%). Trypsin was ineffective under these experimental conditions. Kallikrein-stimulated renin release was completely abolished by trasylol, whereas bradykinin did not increase renin production, indicating that kallikrein's effect is not mediated via kinin generation. There was no demonstrable acid activation or kallikrein activation of the superfusate and chromatography on Sephacryl S-200 revealed a single renin peak of -40,000 mol wt, suggesting that all of the renin release was in the active form. The data suggests that urinary kallikrein acts directly on the rat kidney to release renin, possibly via proteolytic conversion of prorenin to active renin. Our results support the concept that kallikrein may be an endogenous activator of prorenin in the kidney.
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PMID:Direct action of rat urinary kallikrein on rat kidney to release renin. 699 34

Kallikrein is present in the renal tubule near the macula densa, and it has recently been shown to activate inactive renin in human plasma. We recently showed that kallikrein was a potent stimulus of renin release and increased renin secretion in a dose-dependent fashion. To study its effect on renal renin release, we superfused rat renal cortical slices with purified rat urinary kallikrein. Kallikrein-stimulated renin release was completely abolished by trasylol and by amiloride, but was not affected by soybean trypsin inhibitor. Indomethacin did not block kallikrein action, indicating that kallikrein's effect is not mediated via kinin generation and prostaglandins. Kallikrein-stimulated renin release was not blocked by propranolol, trasylol did not block isoproterenol, and dibutyryl cyclic AMP stimulated renin release, indicating that kallikrein may not play a role in the beta-adrenergic mechanism of renin release. There was no demonstrable acid-activatable or kallikrein activatable renin in the superfusate, suggesting that all of the renin release was in the active form. Cathepsin D and plasmin also stimulated renin release from kidney slices in pH 6.0 buffer, whereas trypsin and pepsin did not. Our results support the hypothesis that kallikrein may play a role in the secretion of renin by the kidney. Other proteases can also release renin from the kidney.
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PMID:Direct action of kallikrein and other proteases on the renin-angiotensin system. 702 11

The properties of renin granules isolated from rat renal cortex were studied. Renin granules were thermolabile since in 10 min at 0 degrees C twice as much renin was released as at +37 degrees C. Addition of Ca++ (10(-6) M - 10(-2) M) did not affect the spontaneous release at +37 degrees C, pH 6.5, during 10 or 30 min incubation. However, when pH was elevated to above 7, renin release was significantly increased by Ca++ (10(-3) M). Additions of various amounts of KCl, NaCl or MgCl2, which increased the osmolality less than 20 mOsm/kg, did not affect the stability of the renin granules. Mg-ATP (0.5 and 5 mM) as well as Mg-GTP (5 mM) stabilized renin granules at +37 degrees C, pH 6.5, but the corresponding nitrogen analogues Mg-AMP-PNP and Mg-GMP-PNP (0.5 and 5 mM) were not effective. Neither did Mg-AMP (5 mM) nor ATP (5 mM) without Mg++ affect the renin release. No stabilization was observed by Mg-ATP and Mg-GTP in the purified granule preparations. The results suggest the importance of the cleavage of the terminal phosphate in the stabilization process. When the granules prepared at 300 mOsm/kg were first kept at hyperosmotic medium (range 300-1650 mOsm/kg) and then moved back to 300 mOsm/kg, the granules tend to lyse the more the greater was the reduction of the osmolality. The granules were more stable in isotonic sucrose than in isotonic ionic medium.
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PMID:Further studies on properties of renin granules isolated from rat kidney cortex. 703 14

Prorenin (Pro) is synthesized in a number of human utero-placental tissues, including chorion, decidua, villous placenta and probably mesenchymal cells. The release of Pro from these extra-renal tissues follows new protein synthesis and appears to utilize the constitutive secretory pathway. Unlike processing in the kidney, very little of the Pro is subsequently cleaved to the smaller product (active renin). Primary signals which regulate Pro include protein hormones and peptides (relaxin, endothelin, hCG), amines (epinephrine, norepinephrine, and related beta adrenergic agents), and eicosanoids. These agents increase the mRNA for prorenin at a time before peak secretory effects are noted. Other extracellular signals have negative regulatory effects. These include angiotensin, endotoxin and cytokines (TNF-alpha and interleukin-1 B). There is also evidence that glucocorticoid receptor activation has an inhibitory effects on Pro release in placenta. Second messengers involved in the regulation of Pro include cyclic AMP and protein kinase A (PKA), protein kinase C (PKC), and calcium. The possible biological effect(s) of the extracellular Pro are unknown but may be due to direct generation of angiotensin I. Since angiotensin-peptides have a number of trophic effect on both vascular and non-vascular tissues, regulation of utero-placental Pro by autocrine, paracrine or endocrine signalling may be critical in normal fetal and/or placental development.
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PMID:Regulation of utero-placental prorenin. 748 44

In contrast to cyclic AMP-dependent positive inotropes, the calcium-sensitizer and partial phosphodiesterase (PDE) inhibitor pimobendan may induce beneficial effects in heart failure. However, its effect on relaxation, myocardial energetics and neurohormones are unknown. Twelve patients with heart failure, New York Heart Association (NYHA) classification II-III, due to ischemic cardiomyopathy, were studied for 1 h after they received 5 mg pimobendan intravenously (i.v.). Pimobendan progressively reduced systemic resistance and left ventricular end-diastolic pressure (LVEDP) (22 and 50%, respectively) and improved isovolumetric contractility and relaxation parameters by 30% (all p < 0.05 vs. control). LV end-diastolic and end-systolic volumes (LVEDV, LVESV) decreased significantly by 20 and 19%, respectively. Cardiac output (CO) increased by 17% due to a simultaneous increase in heart rate (HR) from 75 +/- 3 to 86 +/- 5 beats/min (mean +/- SEM, p < 0.05). Pimobendan did not change coronary hemodynamics, but myocardial O2 extraction and consumption were decreased significantly by 18 and 20%, respectively. Catecholamines, angiotensin II (AII), and aldosterone levels did not change significantly. In contrast, arterial and coronary venous renin increased significantly from 57 +/- 17 and 53 +/- 14.7 microM/h at control to 69 +/- 20 and 69 +/- 20 microM/h, respectively, 60 min after pimobendan administration. Simultaneously, cardiac renin uptake at baseline (0.449 +/- 0.185 mumol/min) changed to release (-0.071 +/- 0.145 mumol/min, p < 0.05). Serious side effects did not occur. Thus, pimobendan had progressive positive inotropic and lusitropic effects, diminished preload and afterload despite modest stimulation of plasma renin activity (PRA), and reduced systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic, neurohumoral, and myocardial energetic effects of pimobendan, a novel calcium-sensitizing compound, in patients with mild to moderate heart failure. 753 50

Although adenosine contributes importantly to the regulation of renin release, renal vascular resistance and renal tubular reabsorption, the metabolic pathways that control the intrarenal production rate of adenosine remain ill defined. The objective of this study was to determine whether extracellular metabolism of cyclic AMP to AMP by extracellular phosphodiesterase and hence to adenosine by ecto-5'-nucleotidase can occur in the intact kidney. To test this hypothesis, five experimental series were conducted in kidneys from male Sprague-Dawley rats perfused in a nonrecirculating system (5 ml/min) in vitro with oxygenated Tyrode's solution at 37 degrees C. In each experimental series, cyclic AMP was added to the Tyrode's solution and the renal secretion rates (i.e., the renal venous concentration of purine x the perfusion flow rate) of AMP, adenosine and inosine were determined using high-performance liquid chromatography. In the first experimental series, only cyclic AMP was added to the perfusate. In the second, third, fourth and fifth experimental series, kidneys were perfused with Tyrode's solution containing both cyclic AMP and either 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor), alpha,beta-methyleneadenosine-5'-diphosphate (an ecto-5'-nucleotidase inhibitor), dilazep (an adenosine transport inhibitor) or 1,3-dipropyl-8-p-sulfophenylxanthine (a xanthine that is restricted to the extracellular compartment). In the first experimental series (n = 8), addition of cyclic AMP to the perfusate resulted in significant concentration-related increases in the renal secretion rates of AMP, adenosine and inosine, with the increase in AMP secretion being significantly greater than the increases in adenosine or inosine secretions (delta adenosine secretion/delta AMP secretion = 0.38 +/- 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolism of exogenous cyclic AMP to adenosine in the rat kidney. 753 80

An understanding of the mechanisms involved in the control of the human renin promoter have been hampered and confounded in work to date because of deficiencies in material available and experimental design. The promoter appears to be weak and a good cell model is lacking. Chorio-decidual cultures have been used since these have high renin synthesis, are readily available and grow well in culture. They suffer, however, from phenotypic variability and do not transfect well in transient expression analyses. Recent evidence suggests that 2.6 kb of proximal 5'-flanking DNA is unable to induce native promoter activity under basal conditions. Experiments in which an exogenous enhancer was introduced have raised the possibility that an endogenous enhancer residing outside of the 2.6 kb 5'-flanking region could be required. Cell-type specific factors also appear to be needed. The proximal flanking DNA does, however, appear to be capable of conferring activity on the promoter in chorio-decidual cells under stimulated conditions, suggesting that factors so activated may have considerable importance. Evidence suggests that forskolin-responsive signal transduction pathways may lead cyclic AMP responsive element (CRE) binding protein (CREB) to act on a CRE at -222 in the proximal REN promoter DNA. Activation of the mouse promoter by cAMP appears to involve a different element, however. Furthermore, overall control of renin synthesis is likely to involve post-transcriptional mechanisms as well. Thus, despite being the first cardiovascular gene to be cloned, much more work is required before the control of the human renin gene is fully understood.
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PMID:Function of human renin proximal promoter DNA. 769 94

In this work we analyze the renal and systemic factors involved in the sodium retention in two conditions: in extracellular volume depletion and in edema forming states, particularly liver cirrhosis with ascitis. In this paper we accept that the volume loss of body fluids stimulates the "effective arterial blood volume" (VAE). This term results from a decrease in the arterial blood volume secondary to a fall in cardiac output or a peripheral arterial vasodilatation. The reduction in the VAE stimulates: the high pressure baroreceptors (carotid sinus and aortic arch); the intrarrenal mechanisms, such as the yuxtaglomerular apparatus and the renin angiotensin aldosterone system; the sympathetic adrenergic system; the non osmotic release of antidiuretic hormone; prostaglandins (PGE1, Tromboxane) and endothelin; and inhibits the atrial natriuretic peptide. We also describe the sodium transport mechanisms along the nephron during physiological conditions and after volume depletion, and in edema formation states, specially hepatic cirrhosis with ascitis. We speculate that the intrarenal mechanisms are more important and persistent than the systemic mechanisms. It is possible that the sodium retention of these states might be the result of direct stimuli of the tubular sodium transport mechanisms in the different segments of the nephron, mediated by the co and counter transports, ATPase activity or by the second messengers cyclic AMP and cyclic GMP. The clonation and structural characterization of the different sodium transports may help us to establish, more precisely, the intracellular tubular mechanisms responsible for the tendency of the body to retain sodium. The amount of information generated in the future may help us to demonstrate, with more precision, the mechanisms responsible for the sodium retention and excretion in normal and pathological conditions, particularly the edema forming states such as cardiac failure, nephrotic syndrome and hepatic cirrhosis with ascitis.
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PMID:[Renal and extra-renal mechanisms of sodium and water retention in cirrhosis with ascites]. 777 18


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