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)

Plasma renin activity and aldosterone concentration were determined radioimmunologically after 30 minutes in the left lateral position and after an additional 30 minutes of supine recumbency in 26 normotensive nulliparous women between 28 and 32 weeks' gestation. Plasma renin activity decreased slightly but significantly in the supine position (P less than .05). A distinct increase of plasma aldosterone was observed in 14 of the 26 subjects. The following speculation has been drawn from these results: the fetal renin-angiotensin system is activated by decreased uteroplacental perfusion in the supine position, possibly followed by a diminution of blood flow to the fetal kidney, perhaps via hypoxia. Subsequently, aldosterone may also be secreted by the fetus at an increased rate. In contrast to the high molecular weight renin, aldosterone passes the placental barrier and appears in the maternal circulation.
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PMID:Effect of postural change on plasma renin and aldosterone concentrations in third-trimester pregnancy. 701 18

The differentiation of the juxtaglomerular apparatus in fetuses and newborn mice was investigated by renin immunocytochemistry and electron microscopy. Three to four days before delivery and prior to other organs renin was found in the fetal kidney. At this early time immunoreactivity was preferentially located in cells of the media of interlobular arteries. In newborn mice the formation of new nephrons and maturation of their glomeruli was accompanied by a shift in renin localization from the interlobular arteries to the afferent arterioles. At the same time, kidney renin content and concentration increased rapidly. Synchronously with renin immunoreactivity, during the capillary loop stage of glomerular development, granulated epitheloid cells became visible in the afferent arteriole.
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PMID:Renin immunocytochemistry of the differentiating juxtaglomerular apparatus. 702 7

The role of renal prostaglandin production on the control of renal blood flow (RBF) and renal function was studied in eight chronically catheterized fetal lambs during the last trimester of gestation by using indomethacin as an inhibitor of prostaglandin synthesis. Following administration of indomethacin, RBF decreased significantly (-7.44 +/- 2.04 ml/min) whereas significant increases in filtration fraction (+3.92 +/- 0.85%) and renal vascular resistance (+ 0.41 +/- 0.13 mm Hg . ml-1 . min-1) were observed. Significant changes in glomerular perfusion rate were observed only in the inner portion of the cortex. No changes in GFR were demonstrated. Following administration of indomethacin, significant increases in fetal urinary sodium (+22.2 +/- 7.03 micro E/min) and chloride excretion (+18.2 +/- 6.26 micro E/min) were found despite a decrease in RBF. No changes in potassium excretion were seen. A significant increase in Uosm (+100 +/- 25.9 mOsm/kg H2O) not associated with significant changes in urinary flow rate was also demonstrated following indomethacin. Finally, fetal administration of indomethacin produced a significant decrease in plasma renin activity (-2.70 +/- 0.65 ng/ml/hr) not associated with changes in plasma aldosterone concentration. The present data are consistent with the idea that prostaglandins are important modulators of RBF and renin secretion during fetal life. The inability of indomethacin to render the urine hypertonic indicates that the inability of the fetal kidney to concentrate is probably not due to endogenous activity of the renal prostaglandin system. The increase in sodium chloride excretion with a concomitant reduction of RBF is a pattern not previously reported following inhibition of prostaglandin production. In addition to their effects on RBF and renin release, renal prostaglandins in the fetal kidney may have tubular effects on sodium and chloride absorption that are opposite to those generally ascribed to adult kidneys.
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PMID:Effects of inhibition of prostaglandin synthesis on fetal renal function. 704 93

1. From studies in chronically catheterized fetal sheep and other species, it can be shown that the renin-angiotensin system (RAS) is active during intra-uterine life. Levels of angiotensin II (AII) in fetal sheep are similar to maternal. 2. The fetal RAS plays a role in maintenance of arterial pressure. The extent to which it does so depends on the level of activity of the system. 3. The distribution of renin within the fetal rat kidney is much more widespread than in the adult. The fetal kidney, like other vascular beds has high levels of the AT2 angiotensin receptor subtype. With maturation the proportion of the AT1 receptor subtype increases. 4. Blockade of the fetal RAS with angiotensin converting enzyme (ACE) inhibitors or with the non-peptide AII antagonist (losartan) caused a fall in fetal glomerular filtration rate (GFR) and a rise in renal blood flow (RBF). AII reverses the fall in GFR even though RBF decreases. 5. The fraction of the filtered sodium load reabsorbed by the proximal tubule was not affected when the fetal RAS was blocked by captopril or losartan. High doses of infused AII had no effect on renal reabsorption of sodium, in the short term, but in the long term depressed fractional proximal reabsorption. 6. Only in high doses does AII stimulate the secretion of aldosterone from the fetal adrenal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functions of the renin-angiotensin system during development. 758 4

Within the kidney angiotensin II (Ang II) exerts potent effects on renal function. The intrarenal actions of Ang II include modulation of renal blood flow, glomerular filtration rate, tubular epithelial transport, renin release and cellular growth. The actions of Ang II on the kidney are mediated by specific intrarenal receptors which, based upon physical characteristics and the selective binding of non-peptide and peptide analogs may be divided into two main subtypes, termed AT1 and AT2. AT1 receptors are present within the kidneys of all species and are located predominantly in the glomerulus, the renal tubules and the renal vasculature, including the afferent and efferent arterioles. Modulation of AT1 receptors within the kidney has been shown to mediate essentially all of the known intrarenal effects of Ang II. AT1 receptors and particularly AT2 receptors are expressed in large numbers in fetal kidney where they may play a role in development and maturation. In some species, intrarenal AT2 receptors disappear shortly after birth. In those species where AT2 receptors are present in the adult kidney their role in the control of renal function has not yet been clearly defined.
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PMID:Pharmacology of angiotensin II receptors in the kidney. 769 86

The renin-angiotensin system is activated during vascular development and injury. Furthermore, angiotensin II (Ang II) is a comitogen for fetal mesangial cells in vitro and it may be important in vascular smooth cell growth in disease states. Since fibronectin is an important extracellular matrix protein for vascular development and it too is overexpressed in the mesangium of diseased glomeruli, we explored the interrelationship of fibronectin and Ang II in fetal mesangial cell growth. In human fetal kidney, Ang II type 2 receptors (AT2) were detected in abundance by ex vivo autoradiography. When mesangial cells were isolated from fetal kidney and grown in culture, Ang II type 1 receptors (AT1) were also detected. To explore the mitogenic properties Ang II and fibronectin as well as the effects of Ang II on fibronectin metabolism, studies were performed in vitro, isolated from the potentially confounding variables of hemodynamic influence and circulating growth factors and cytokines. In vitro, mesangial cells expressed a single class of AT1 receptors that were not altered by growth on various substrates. Ang II (10(-7) M) significantly increased thymidine incorporation by confluent human fetal mesangial cells (twofold). When subconfluent, Ang II-stimulated proliferation was greater (fourfold). Ang II significantly increased cell-associated and secreted fibronectin as determined by immunoprecipitation at concentrations that also stimulate mitogenesis. Both of these Ang II-mediated responses were inhibited by the AT1 receptor antagonist DuP-753 (10(-5) M) but not by AT2 receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin II stimulates human fetal mesangial cell proliferation and fibronectin biosynthesis by binding to AT1 receptors. 812 7

Renin is first observed in the 14-day fetal kidney. There is a sharp increase in the number of renin positive cells in the 15-day fetal kidney. Renin is located in the smooth muscle cells of arterioles, interlobular arteries, and branches of the renal artery. In the neonatal kidney, the amount of renin appears to be equal to that observed in the 15-day fetal kidney and is still located in the same blood vessels. In the 24-hour postnatal kidney, there is a sharp decrease in the total amount of renin. Renin positive cells are now observed at the vascular pole. In the 48-hour postnatal kidney, there is a sharp increase in the total amount of renin. Most of the renin positive cells are located at the vascular poles; however, a few renin positive cells are seen in the interlobular arteries.
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PMID:Sites of renin production in fetal, neonatal, and postnatal Syrian hamster kidneys. 841 23

In this article, we have discussed the localization of components of the renal renin-angiotensin system, as well as the existing information on the regulation of this axis and the effects of Ang II on renal function. All the components of the renin-angiotensin system are present in both fetal and adult kidney. In the adult kidney, renin is principally localized to jg cells of the distal afferent arteriole, where release is stimulated by increases in intracellular cAMP and inhibited by increases in cytosolic calcium. Four distinct stimuli mediating renin release are (1) NaCl sensed at the macula densa, (2) the sympathetic nervous system, (3) humoral factors, with Ang II, vasopressin, endothelin, and adenosine inhibiting renin release, and (4) changes in intrarenal blood pressure. Alterations in renal renin gene expression have been reported in pathophysiological states, such as salt depletion, diabetes mellitus, ureteral obstruction, Bartter's syndrome, and with high protein feeding. The highest renal concentrations of mRNA for the renin substrate angiotensinogen are found in the PT, where the protein is localized to subapical granules. Both salt depletion and androgens upregulate renal angiotensinogen mRNA. Of interest, renal angiotensinogen mRNA levels are lower in SHR than in normotensive WKY rats. As with angiotensinogen, renal ACE is mainly localized to the PT, with highest concentration on the brush border. The mechanisms of regulation of both renal angiotensinogen and ACE require further study. Using recently developed specific nonpeptide Ang II receptor antagonists, it appears that adult renal Ang II receptors are principally of the AT1 class, whereas fetal kidney Ang II receptors are of the AT2 subtype. By binding to AT1 receptors, Ang II exerts constrictive effects on both afferent and efferent arterioles, with increased effect reported on efferent arterioles. Glomerular Ang II receptors are localized to mesangial cells, mediating contractile responses resulting in changes in glomerular surface area and Kf, and potentially regulating mesangial sieving and phagocytosis. These receptors are reduced with salt restriction or in experimental diabetes. The highest concentrations of tubular Ang II receptors are found in PT, on both brush border and basolateral membranes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The intrarenal renin-angiotensin system. 843 83

1. The angiotensin type 1 (AT1) receptor antagonist, losartan (10 mg/kg) was infused intravenously into nine chronically catheterized fetal sheep (125-132 days gestation). Losartan reduced the fetal systolic (P <0.01) and diastolic (P <0.01) pressor response to 5 microg angiotensin II (AngII) i.v. from 27.4 +/- 1.5 to 7.4+/-0.9 and from 17.5 +/- 1.3 to 5.4 +/- 0.6 mmHg, respectively, after 1 h and to 6.1 +/- 0.5 and 4.4 +/- 0.5 mmHg, respectively, after 2 h. Maternal pressor responses to 5 microg AngII i.v. were unchanged. Fetal mean arterial pressure decreased (P <0.05) after losartan administration, but fetal heart rate did not change. 2. Fetal haematocrit increased (P <0.05), fetal PO2 decreased (P <0.01), PCO2 did not change and pH decreased (P <0.01), as did plasma bicarbonate levels (P <0.01) following administration of losartan. Thus, losartan induced a fetal metabolic acidosis. 3. Fetal placental blood flow did not change following administration of losartan. In the fetal kidney, losartan caused a decrease in vascular resistance (P <0.01) and an increase in blood flow (P <0.05). Glomerular filtration rate decreased (P <0.05); thus, filtration fraction decreased (P <0.01). There was no change in the fractional reabsorption of sodium and glomerulotubular balance was maintained. Free water clearance decreased (P <0.01) and became negative. Urine flow decreased (P <0.01), the excretion rates of sodium, potassium and chloride did not change, but the urinary sodium: potassium ratio decreased (P <0.05). There was a decrease in lung liquid flow (P <0.05) following losartan. 4. It is concluded that the fetal renin-angiotensin system (RAS) is important in the maintenance of fetal arterial pressure, the regulation of fetal renal blood flow and is essential in the maintenance of fetal glomerular function. Further, these actions of AngII are mediated via functional AT1 receptors. These effects of losartan on the fetal cardiovascular system, renal blood flow and function are similar to those observed following captopril administration. Thus, the effects of angiotensin converting enzyme (ACE) inhibition in the foetus are due to the blockade of the fetal RAS and are independent of any direct effects on bradykinin or prostaglandin levels.
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PMID:Effects of losartan on the cardiovascular system, renal haemodynamics and function and lung liquid flow in fetal sheep. 881 40

Fetal rat kidney contains renin in renal microvasculature, whereas adult rat kidney contains renin predominantly in juxtaglomerular cells. It is hypothesized that renin isoforms stored within these renal tissues may differ chemically and functionally. To test this hypothesis, stored renin isoforms in fetal and adult rat kidney were compared by isolating renin from adult and fetal kidney homogenate with pepstatin agarose. Pepstatin-eluted renin isoforms were separated by relative molecular size using one-dimensional polyacrylamide gel electrophoresis (SDS-PAGE), or by isoelectric point (pI) and size using two-dimensional (2D) gel electrophoresis. Isoforms were identified either by silver staining or immunoblotting. One-dimensional polyacrylamide gel electrophoresis of pepstatin-treated kidney homogenates showed a silver-stained band in the range of approximately 45 kDa, which corresponded to a silver-stained spot consistently seen on 2D gels. In fetal kidney homogenate, the approximately 45 kDa band had a pI of 5.3 +/- 0.1, whereas the corresponding band in adult samples had a basic pI of 6.0 +/- 0.05. Angiotensin I generation was measured to assess renin enzymatic activity. There was significantly more inactive renin in fetal kidney homogenate than in adult kidney homogenate (60.2 +/- 22.4 v 9.6 +/- 4.0 ng AI/mg protein/h, P < .05). There was significantly less active renin in fetal kidney homogenate than in adult kidney homogenate (5.4 +/- 0.4 v 36.5 +/- 14.2 ng AI/mg protein/h, P < .05). The average total renin activity in fetal kidney homogenate was significantly higher than in adult kidney homogenate (65.6 +/- 22.3 v 46.0 +/- 15.2, P < .05). These results demonstrate major differences in the physical and enzymatic forms of stored renin found in fetal and adult kidney. It is speculated that these variations in stored renin isoforms play a role in the developmental differential regulation of the intrarenal renin angiotensin system.
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PMID:Stored renin isoforms in the developing rat kidney. 952 51


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