Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Hypertension hyponatremia syndrome occurred in a 32-week male neonate following septicemic shock on Day 9. The systolic blood pressure rose from 60 to 85 mmHg as the serum sodium dropped from 136 to 121 mmol/L associated with natriuresis, polyuria, and dehydration. Convulsions occurred at a systolic blood pressure of 102 mmHg. Investigations for hypertension revealed hyper-reninemia without cardio/renovascular or neuroendocrine abnormalities. Salt supplementation and antihypertensive therapy with captopril led to resolution of natriuresis and hyponatremia. Review of literature revealed associated renovascular pathology in all neonatal cases of the syndrome reported so far. Renal ischemia from possible renal microthrombi may have been the triggering event in our case. Decline in renin levels during follow-up favors this hypothesis.
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PMID:Hypertension-hyponatremia syndrome in neonates: case report and review of literature. 1077 96

An intracardiac aldosterone system which responds to short- and long-term physiological stimuli has been described. This cardiac generated aldosterone has possibly autocrine or paracrine actions. Normal cardiac tissue contains mineralocorticoid receptors (MR) and cardiac high affinity MR are localized in cardiac myocytes and endothelial cells. Data concerning the presence of MR in cardiac fibroblasts are, however, controversial. MR are not specific for aldosterone but they also bind glucocorticoids. Cardiac fibroblasts however contain the enzyme 11beta-hydroxy-steroid dehydrogenase II which converts these glucocorticoids to inactive metabolites. Discordant findings on the in vitro effect of aldosterone on the collagen synthesis in cardiac fibroblasts are reported and can at least partly attributed to the presence of various fibroblasts phenotypes. During chronic aldosterone infusion in uninephrectomized rats on a high-salt diet, a marked accumulation of interstitial and to a lesser extent perivascular collagen occurs in the heart in both ventricles. This cardiac fibrosis in this aldosteronism model is prevented by spironolactone. This effect of aldosterone is crucially dependent on the salt status of the rat. Indeed, rats on a restricted salt intake infused with aldosterone had no cardiac fibrosis above control levels. During the continuous infusion of aldosterone in the rat the appearance of fibrosis was delayed and starts 4 weeks after the beginning of the infusion which argues against a direct effect of aldosterone. The mechanism of aldosterone-salt induced cardiac fibrosis possibly involves angiotensin II acting through upregulated AT1 receptors and the cardiac AT1 receptor is the target for aldosterone. An accumulation of collagen in the heart has also been found in patients with adrenal adenomas and during chronic activation of the renin-angiotensin-aldosterone system such as in surgically induced unilateral renal ischemia, unilateral renal artery banding or renovascular hypertension. Spironolactone prevents aortic collagen accumulation in spontaneously hypertensive rats. In patients with stable chronic heart failure spironolactone treatment in addition to diuretics and angiotensin-converting enzyme (ACE) inhibition reduced circulating levels of procollagen type III N-terminal aminopeptide. Also, in the Randomized Aldactone Evaluation Study spironolactone coadministered with conventional therapy of ACE inhibitors, loop diuretics and digitalis in patients with symptomatic heart failure defined as NYHA classes III-IV reduces total mortality by 30%.
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PMID:Induction of cardiac fibrosis by aldosterone. 1088 42

The present study determined the effect of either occlusion of the left renal artery for 60 min (ischemia) or sham operation on angiotensin (ANG) receptors and tissue and urinary levels of ANG peptides between 24 and 72 h recovery in male Sprague-Dawley rats. At 24 h postischemia, urinary concentrations of ANG I and ANG-(1-7) rose by an average of 83 and 64%, respectively (P < 0.05) but had declined to control levels by 72 h. Tissue ANG II rose at 24 h in postischemic kidneys by an average of 63% compared with the contralateral nonischemic kidney (P < 0.05). Whereas the enzymatic activity of angiotensin-converting enzyme and neprilysin was reduced after ischemia, renal renin activity in ischemic kidneys rose by 74% compared with sham-operated kidneys. Receptor autoradiography using (125)I-labeled [Sar(1),Thr(8)]ANG II ((125)I-Sarthran) (0.8 nM) revealed a decreased apparent density of ANG receptors (>80% AT(1)) in ischemic kidneys with a trend for a decrease in the contralateral nonischemic kidneys compared with the kidneys from sham-operated rats. Twenty-four hours after ischemia, ANG II receptors decreased by 68% in glomeruli (P < 0.05), 49% in the outer cortical tubulointerstitial area (P < 0.05), and 48% in the inner cortical-outer medullary area of the vasa recta (P < 0.05). Medullary binding decreased approximately 50% in both the ischemic kidney and the contralateral nonischemic kidney compared with sham. In all regions of the ischemic kidney, receptors recovered by 72 h to levels not different from sham control rats. The marked change in urinary ANG I and ANG-(1-7) at 24 h following occlusion indicates these peptides may be potential urinary markers for acute renal ischemia. The reduction of receptors in vascular and tubular regions of the ischemic kidney provides a mechanism for the loss of vasoconstrictor responses to ANG II following ischemia previously reported by others.
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PMID:Differential actions of renal ischemic injury on the intrarenal angiotensin system. 1099 13

Pharmacological interruption or genetic disruption of the renin-angiotensin system before completion of nephrogenesis produces papillary atrophy and an impaired urinary concentrating ability. The mechanisms involved are yet to be elucidated, but renal hypoperfusion and subsequent ischemia, particularly to the immature renal medulla, may be hypothesized. The acute intrarenal responses to angiotensin-converting enzyme (ACE) inhibition in the newborn piglet were thus investigated by means of regional blood flow distribution, renal interstitial hydrostatic pressure (RIHP), and medullary oxygen tension (PO2) in the anesthetised 4- to 5-day-old piglet. Moreover, the calcium antagonist nifedipine and the nitric oxide synthesis inhibitor L-NAME were also given in order to reduce renal blood flow by other means. The drugs were given intravenously in equipotent pressor doses, mimicking intraperitoneal injections in neonatal rats. Enalaprilat (200 microg/kg) reduced mean arterial pressure (MAP) by 14+/-10% (mean+/-SD, P=0.006) and RIHP by 18+/-18% (P=0.001), whereas total renal blood flow and medullary PO2 remained unchanged. In contrast, nifedipine (0.5 mg/kg) reduced MAP and RIHP by 39+/-8% and 38+/-14%, respectively, total and regional blood flows by 30%-60%, and medullary PO, by 46+/-29% (P=0.001). Acute administration of L-NAME (15 mg/kg) increased MAP by 27+/-10% (P=0.0005), whereas RIHP and renal blood flow decreased by 20%-50%, resulting in a reduction of the medullary PO2 by 10+/-12% (P=0.05). We conclude that the renal abnormalities observed after neonatal ACE inhibition are not likely to be caused by renal ischemia.
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PMID:Acute renal responses to angiotensin-converting enzyme inhibition in the neonatal pig. 1104 89

Vascular endothelial growth factor (VEGF) is transcribed in the VEGF(120), VEGF(164), or VEGF(188) isoforms, which differ in receptor binding, matrix association, and angiogenic activity. This vascular growth factor has been implicated in the development of the renal vasculature, but the role of the distinct VEGF isoforms remains unknown. In the present report, renal angiogenesis and arteriogenesis were studied in VEGF(120/120) mice, expressing only the short VEGF(120) isoform. In VEGF(120/120) mice, ingrowth and survival of capillaries in glomeruli, remodeling of peritubular capillaries, vascular coverage by pericytes, and branching of renal arteries were all severely impaired, causing abnormal glomerular filtration and impairing renal function. The arterial branching defect might be related to a reduced expression of renin, a presumed renal arterial branching factor. Glomerulosclerosis and tubular dilation possibly resulted from renal ischemia caused by vascular defects. Thus, VEGF(164) and VEGF(188) not only mediate angiogenesis, but they also play an essential role in renal branching arteriogenesis.
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PMID:Loss of the VEGF(164) and VEGF(188) isoforms impairs postnatal glomerular angiogenesis and renal arteriogenesis in mice. 1203 84

The renin-angiotensin system is initiate by numerous pathological situations which release the renal ischemia: heart failure, arterial hypertension, renal pathology with or without diabetes mellitus. Therapeutic possibilities in renin-angiotensin system control are offered by angiotensin-converting enzyme inhibitors, angiotensin II type-1 receptors antagonists, angiotensin converting enzyme inhibitors and neutral endopeptidase inhibitors and angiotensin II type 2 receptors agonists.
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PMID:[The renin-angiotensin system:implications, pathology, therapeutic possibilities, perspectives]. 1209 17

Chronic renal ischemia caused by atherosclerotic renal artery stenosis (RAS) is gaining recognition as a potentially important risk factor for cardiovascular (CV) morbidity and mortality. The etiology of increased risk of CV events is multifaceted and includes direct physiologic changes that increase risk as well as intermediate clinical effects that are associated with worse outcome. Physiologic changes associated with increased CV risk in patients with RAS include increased production of fibrogenic and vasoactive peptides such as renin, angiotensin, endothelin, and catecholamines, as well as endothelial cell dysfunction. Clinical intermediate conditions associated with higher incidences of CV events seen in patients with renal ischemia include hypertension, systemic atherosclerosis, chronic renal failure, and left ventricular hypertrophy and dysfunction. More thorough understanding of the myriad physiologic changes seen in patients with RAS will likely improve patient selection for renal artery revascularization. Clinical trials should examine a full range of CV and renal outcomes, not just blood pressure, to adequately assess the merits of revascularization.
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PMID:Chronic renal ischemia: implications for cardiovascular disease risk. 1247 Nov 81

Autosomal dominant polycystic kidney disease (ADPKD), a common genetic disease, is characterized by the development of hypertension and end stage renal disease. An increase in the activity of the renin-angiotensin system, due to a renal ischemia caused by cyst expansion, contributes to the development of hypertension and renal failure in ADPKD. Recently, the angiotensinogen (AGT) gene, M235T, and angiotensin II type 1 receptor (ATR) gene, A1166C, polymorphisms have been associated with the susceptibility to develop hypertension and renal disease. We hypothesized that the AGT M235T and ATR A1166C polymorphisms could account for some of the variability in the progression of ADPKD. Genotyping was performed in 108 adult patients with ADPKD, and 105 normotensive healthy controls, using PCR and restriction digestion. We analyzed the effects of the AGT M235T and ATR A1166C polymorphisms on hypertension and age at the end stage renal disease (ESRD). Of the 108 patients with ADPKD, 64 (59%) had hypertension and 24 (22%) reached the ESRD. The prevalence of hypertension were; [MM+MT], [TT] genotypes, 60%, 59% (p=1.00); [AA], [AC+CC] genotypes, 60%, 50% respectively (p=0.54). The ages at the onset of ESRD were; [MM+MT], [TT] genotypes, 50 +/- 9 years, 56 +/- 8 years (p=0.07); [AA], [AC+CC] genotypes, 54 +/- 8 years, 52 +/- 14 years, respectively (p=0.07). There were no differences in the prevalence of hypertension and the ages at the ESRD in relation to the AGT M235T and ATR A1166C polymorphisms. We suggest that the AGT and ATR gene polymorphisms would not have an effect on hypertension or the ESRD in ADPKD.
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PMID:Angiotensinogen and angiotensin II type 1 receptor gene polymorphism in patients with autosomal dominant polycystic kidney disease: effect on hypertension and ESRD. 1295 Jan 20

Functional angiotensin II receptors have been documented in cardiac fibroblasts as well as an intracardiac aldosterone system that responds to short- and long-term physiological stimuli. In vitro, angiotensin II increased cardiac fibroblast-mediated collagen synthesis and mRNA levels of collagen type I, type III, pro-alpha1 (I) collagen, pro-alpha1 (III) collagen and fibronectin, and inhibited matrix metalloproteinase I activity. The angiotensin II-stimulated secretion and expression of collagen was completely abolished by AT1 receptor antagonism, but not affected by AT2 receptor antagonism. In vivo, chronic infusion of angiotensin II increased the collagen volume fraction in the ventricles. Angiotensin-converting enzyme (ACE) inhibition and AT1 receptor antagonism, but not AT2 receptor antagonism, reduced collagen deposition in the myocardium in spontaneously hypertensive rats and in rat myocardium following myocardial infarction. During chronic aldosterone infusion in uninephrectomized rats on a high-salt diet, a marked accumulation of interstitial and to a lesser extent perivascular collagen occurs in the heart in both ventricles. The cardiac fibrosis in this aldosterone model is prevented by spironolactone. During the continuous infusion of aldosterone in the rat, the appearance of fibrosis was delayed and started 4 weeks after the beginning of the infusion, which argues against a direct effect of aldosterone. The mechanism of aldosterone-salt-induced cardiac fibrosis possibly involves angiotensin II acting through upregulated AT1 receptors and the cardiac AT1 receptor is the target for aldosterone. An accumulation of collagen in the heart has also been found in patients with adrenal adenomas and during chronic activation of the renin-angiotensin-aldosterone system such as in surgically-induced unilateral renal ischemia, unilateral renal artery banding or renovascular hypertension. Spironolactone prevents aortic collagen accumulation in spontaneously hypertensive rats. In patients with stable chronic heart failure, spironolactone treatment in addition to diuretics and ACE inhibition reduced circulating levels of procollagen type III N-terminal aminopeptide. Also, in the Randomized Aldactone Evaluation Study, spironolactone coadministered with conventional therapy of ACE inhibitors, loop diuretics and digitalis in patients with symptomatic heart failure defined as NYHA classes III-IV, reduced total mortality by 30%.
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PMID:Role of intracardiac renin-angiotensin-aldosterone system in extracellular matrix remodeling. 1457 Dec 85

Since hepatorenal syndrome is a functional renal failure due to renal ischemia in cirrhotics with refractory ascites, we investigated whether increased intra-abdominal pressure (IAP) impairs the renal function and perfusion in cirrhotic portal hypertensive rats. Eight groups of 32 rats each were studied, including 4 control and 4 CCl(4) cirrhotic groups. These were subdivided into two groups each, with and without an increased IAP, and further subdivided into groups of rats with and without NO inhibition. IAP was increased to 20 mm Hg for 7 consecutive days by means of an intraperitoneally placed balloon filled with water. The animals were studied in normal conditions and after inhibition of NO synthesis. Changes in mean arterial pressure and renal microcirculation by means of femoral artery catheterization and laser-Doppler technique, respectively, were recorded. Venous samples for determination of plasma renin-aldosterone activity, biochemical parameters of liver and renal function, and plasma nitrite/nitrate levels as an index of NO synthesis were drawn. Cirrhotic rats showed decreased renal microcirculation (P = 0.05), while elevated IAP produced a further decrease (P = 0.01). Renin-aldosterone levels found increased (P = 0.001) in cirrhotics, and elevated IAP produced a further increase (P = 0.01] in both groups. Inhibition of NO synthesis resulted in a nonsignificant decrease in both renal microcirculation and renin-aldosterone levels in all experimental groups. Liver and renal function was found to be impaired in cirrhotics, but increased IAP had a nonsignificant further functional impairment in both organs. In conclusion, chronically elevated IAP in cirrhotic rats is associated with an increase in renin-aldosterone levels and significant impairment of renal perfusion.
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PMID:The influence of continuous seven-day elevated intra-abdominal pressure in the renal perfusion in cirrhotic rats. 1457 84


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