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

The demonstration that the components required for the generation of angiotensin II are present in the brain has led to the proposal that there is a brain renin-angiotensin system. To test this hypothesis, experiments were performed to determine if biologically active amounts of angiotensin II are formed when renin is injected into the cerebral ventricles. The effects of central administration of agents known to block the peripheral renin-angiotensin system were also investigated. It was shown that intraventricular renin increased water intake, blood pressure and ADH secretion and that these effects were blocked by saralasin. These findings indicated an interaction between injected renin, brain angiotensinogen and converting enzyme, resulting in the formation of angiotensin II in physiologically active concentrations. However, these experiments did not demonstrate a role for endogenous brain renin activity. Central administration of saralasin in normal animals did not decrease water intake, blood pressure or ADH secretion. These studies thus failed to demonstrate a physiological role for the proposed brain renin-angiotensin system in controlling water balance and blood pressure.
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PMID:The use of saralasin to evaluate the function of the brain renin-angiotensin system. 101 60

1. The possible inhibitory effect of des-angiotensin I substrate on the renin-substrate reaction was studied. For this purpose rat angiotensinogen was purified 50-fool from plasma of nephrectomized rats. Des-angiotensin substrate was prepared from the purified angiotensinogen preparation by reaction with immobilized hog renin (coupled to Sepharose). 2. In kinetic experiments it was found that desangiotensin I substrate in concentrations of 0-225 and 0-45 micronmol/l has no influence on the reaction between rat renin and rat angiotensinogen.
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PMID:Evidence against inhibition of the renin-angiotensinogen reaction by des-angiotensin substrate in the rat. 107 95

A naturally occurring competitive inhibitor of pig kidney renin has been identified in human plasma. The inhibitor was shown to be alpha-1 anti-trypsin and the effect in vitro on the renin activity was examined. The slope in the Hill plot is compatible with the assumption of one-site competitive inhibition. Other proteinase inhibitors, such as alpha-2-macroglobulin and C1 inactivator, however, have no inhibitory effect on the renin-angiotensinogen reaction.
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PMID:alpha-1-Anti-trypsin, an inhibitor of renin. 108 51

Effects of unilateral nephrectomy on plasma renin concentration and renin substrate (angiotensinogen) concentration were studied over an experimental period of 10 days in rats. The maximum increase in plasma renin substrate concentration after bilateral nephrectomy was 9 times higher than the preoperative level. Very low but measureable plasma renin concentrations were found in rats nephrectomized bilaterally 24 hrs previously. In unilateral nephrectomized rats the concentration of renin substrate in plasma increased maximumly 3.5-fold within 24 hrs after the operation and on the third day it was decreased to half of the maximum level. Even 10 days after uninephrectomy the concentration of plasma renin substrate was significantly higher than that of normal rats. Twenty four hours after unilateral nephrectomy plasma renin concentration decreased to similar low levels as those found in bilateral nephrectomized rats. The decreased concentration of plasma renin, however, returned to normal 3 days after uninephrectomy. The inverse relationship was seen between the concentrations of plasma renin and plasma renin substrate. However, substrate concentration in plasma rised faster and longer than plasma renin decreased.
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PMID:Effects of unilateral nephrectomy on plasma renin substrate and renin concentration in rats. 117 13

The aim of the present investigation was to (a) determine if renin-substrate (angiotensinogen) is present in cerebrospinal fluid; (b) investigate the effects of intracerebroventricular administration of renin on drinking and blood pressure; and (c) determine if such effects are mediated via the formation of angiotensin II. Angiotensinogen concentration in cerebrospinal fluid was measured in 15 dogs and averaged 205 +/- 34 ng/ml. This value was approximately 1/5th of the corresponding plasma angiotensinogen concentration but the ratio of angiotensinogen:total protein in cerebrospinal fluid was approximately 15 times greater than in plasma. Intraventricular injection of hog renin (0.1 Goldblatt units) stimulated drinking in each of 8 dogs; the mean volume drunk in the 15 min period following the injection was 485 +/- 84 ml. When the renin was preceded by intraventricular saralasin acetate, a specific antagonist of angiotensin II, the drinking response was reduced to 8 +/- 6 ml. In eight pentobarbital anesthetized dogs, intraventricular dog or hog renin (0.05-0.25 Goldblatt units) increased systolic pressure from 152 +/- 10 to 168 +/- 10 mm Hg (P less than 0.001) and diastolic pressure from 101 +/- 8 to 116 +/- 7 mm Hg (P less than 0.001). This response, which lasted from 30 min to more than 3 h, was also abolished by saralasin acetate. These data indicate that centrally administered renin increases drinking and blood pressure and that these effects are mediated via the formation of angiotensin II.
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PMID:The effects of intracerebroventricular administration of renin on drinking and blood pressure. 117 5

In order to verify the possibility than human plasma and kidney can activate a renin preinhibitor (Phospholipid) into inhibitor (lysophospholipid), constant quantities of preinhibitor were added to plasma and kidney homogenate. Addition of preinhibitor to plasma did not modify the quantity of Angiotensin I that developed. On the other hand, addition of preinhibitor to crude kidney homogenate, followed by incubation with human angiotensinogen, caused a significant fall in the quantity of Angiotensin I generated. While plasma is deficient in the specific enzyme delegated to the transformation of preinhibitor into inhibitor, it appears that this enzyme is present in the kidney.
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PMID:A possible role of the kidney in activating a renin preinhibitor. 121 65

Literature examining angiotensinogen, a substrate of renin which forms the decapeptide angiotensin I which, in turn, forms the octapeptide angiotensin II, is surveyed. The regulation of the formation of angiotensinogen is thought to take place in the liver, but efforts to confirm this have been unsuccessful. The gonadotropic function of the hypophysis has been determined to have an influence on the level of angiotensinogen in the plasma. Much attention has been given to the adrenal glands as regulators of the formation of angiotensinogen in the liver. The sexual hormones have been thought to have a great influence on the regulation of angiotensinogen and are examined in regard to the influence of estrogens on the content of it in the plasma and to the hormonal regulation of the disruption of it, which takes place through hormonal regulation of the speed of renin secretion. The hormonal regulation of the excretion of angiotensinogen is shown diagrammatically.
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PMID:[Hormonal regulation of the level of angiotensinogen in the blood plasma]. 122 55

The purpose of this study was to determine whether centrally administered renin stimulated vasopressin secretion. Vasopressin was not measured directly, but, instead, changes in urinary water excretion in anesthesized dogs undergoing a water excretion in anesthetized dogs undergoing a water diuresis were used as an index of changes in vasopressin secretion. Intraventricular injection of hog renin in a dose of 0.1 Goldblatt unit produced a marked decrease in urine flow which was associated with a decrease in free water clearance and an increase in urinary osmolatiy with no change in osmolar clearance. Sodium excretion increased significantly but there was no change in potassium excretion. These effects, which closely resemble those resulting from an increase in vasopressin secretion, were prevented by hypophysectomy. The antidiuretic effect clearly resulted from an action of renin in the central nervous system since renin had no effect on urine flow or osmolality when administered intravenously. Intraventricular administration of saralasin acetate, a specific antagonist of angiotensin II, completely blocked the effects of intraventricular renin indicating that these effects were mediated via the formation of angiotensin II. The data therefore indicate that there is an interaction between injected renin, brain angiotensinogen, and converting enzyme resulting in the formation of angiotensin II which stimulates the secretion of vasopressin. Additional studies are required to determine whether the brain renin-angiotensin system plays a physiological role in the regulation of a vasopressin secretion.
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PMID:Antidiuresis produced by injection of renin into the third cerebral ventricle of the dog. 124 51

In vascular smooth muscle cell (VSMC) cultures from Sprague-Dawley (SD) and hypertensive transgenic rats for the mouse renin gene Ren-2 (TGR), the DNA synthesis, which was analyzed by the uptake of [3H]thymidine, was higher in TGR than SD VSMCs (2.5- to 8-fold, mean of 5.6-fold) under basal conditions. DNA synthesis was increased by fetal calf serum (10%) in SD cells more than in TGR VSMCs, and was decreased by heparin (400 micrograms/ml) and by phorbol-12,13-dibutyrate (10(-7) M) in TGR VSMCs to a higher degree than in SD cells. Neither endothelin (10(-7) M), angiotensinogen (10(-8) M), the renin inhibitor CGP 29,287 (10(-4) M), angiotensin I (10(-7) M), captopril (10(-5) M), angiotensin II (10(-7) M), nor saralasin (10(-6) M) modified DNA synthesis in either type of VSMCs. Sodium nitroprusside (10(-4) and 10(-3) M) increased DNA synthesis in both kinds of VSMCs but in TGR cultures it became toxic at 10(-3) M. 8-Bromocyclic GMP (10(-7) to 10(-5) M) reduced DNA synthesis in SD cells more than in TGR VSMCs. These results suggest that (a) cellular mechanisms of proliferation appear to be more activated in TGR VSMCs, likely involving a protein kinase C-dependent pathway but not the renin-angiotensin system, and (b) in both type of cells, sodium nitroprusside possesses proliferative properties whereas 8-bromocyclic GMP has antiproliferative properties.
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PMID:Vascular smooth muscle proliferation in hypertensive transgenic rats. 128 47

ACE-inhibitors improve symptoms and prognosis in patients with heart failure. The V-Heft II trial has demonstrated that the beneficial effect of these agents is superior to unspecific vasodilators. Besides sustained arterial and venous vasodilation the inhibition of the neurohumoral axis is thought to play an important role. Angiotensin II and catecholamines not only exert vasoconstrictor effects, but might also contribute to vascular and myocardial growth. Thus, it may not be surprising that the beneficial effects of ACE inhibitors in heart failure only emerge during long-term therapy rather than after short-term administration. It has been shown that these agents improve blood flow to skeletal muscle during exercise after chronic therapy (not acutely), and there is some preliminary evidence that improvement of endothelial function might be involved in this effect, i.e., by reducing the degradation of bradykinin, an endothelial vasodilator. ACE inhibitors reduce LV hypertrophy, an important risk factor for cardiovascular disease and prognosis. Moreover, there is experimental evidence that ACE inhibitors can prevent and even reverse interstitial fibrosis in the left ventricle. Although the plasma renin activity may be normal in patients with chronic heart failure, recent data using polymerase chain reaction indicate that the tissue cardiac renin angiotensin system is activated in the failing human heart as assessed by measurements of angiotensin converting enzyme mRNA and angiotensinogen mRNA which may be an important target for ACE-inhibition.
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PMID:[The value of ACE inhibitors in heart failure (mechanism of action)]. 129 Mar 8


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