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)

Peripolar cells are granulated glomerular epithelial cells that form a cuff around the vascular pole of the glomerulus. Quantitation of these cells in 17 species of mammals (including man, several laboratory animals and a variety of other species) indicated that they were detectable by light microscopy in all but one of the mammals that were examined (the Australian hopping mouse). In adult mammals with detectable peripolar cells, the "peripolar cell index" (the percentage of randomly sectioned glomeruli that displayed peripolar cells in histological sections of kidney) ranged from 0.15 (for echidna) to 11.86 (for sheep). Newborn lambs and rats showed strikingly high values (23.30 and 10.76, respectively) compared with their adult counterparts. Using electron microscopy, peripolar cells were observed in all species that were examined, including the Australian hopping mouse. Morphologically, peripolar cells were similar in all species although their size and granule population varied. They showed a predominantly outer cortical glomerular distribution and a close anatomical relationship with the renin-containing myo-epithelioid cells. These findings indicate that peripolar cells are present in a wide variety of species and support the view that such cells may play a significant role in the regulation of normal renal function.
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PMID:Distribution of glomerular peripolar cells in different mammalian species. 369 86

Using hybridization histochemistry renin gene expression has been localized in the juxtaglomerular apparatus (JGA) of the renal cortex in both mouse and sheep kidney. This technique also located renin gene expression in afferent arterioles and interlobular arteries distant from the glomerular tuft in lamb renal cortex. A short (30 mer) synthetic oligonucleotide probe, complementary to a region of the mouse submaxillary gland renin gene, specifically labelled mouse submaxillary gland and kidney. Hybridization histochemistry and Northern blot analysis using both the synthetic oligonucleotide (mouse) probe and a 700 base pair recombinant (sheep) probe showed differences in renin gene expression in the kidney in response to Na restriction in the mouse and Na depletion in the sheep.
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PMID:Use of synthetic oligonucleotide and recombinant DNA probes to study renin gene expression. 389 92

Close afferent arteriolar (AA) connectivity is a prerequisite for hemodynamic interaction between superficial rat nephrons. Studies were conducted in rat, mouse, rabbit, and human renal vasculatures obtained by an HCl maceration-microdissection technique to document the extent of AA connectivity. In rat kidneys, we assessed the possibility for a slow component of internephron coupling, as reflected by arteriolar renin cell distribution after specific immunostaining for renin. In the four species examined, 51% (human) to 60% (mouse) of total AA populations were organized as vascular units consisting of mostly two AA sharing a common origin and a connecting arterial segment. In rat AA pairs, branch lengths were significantly correlated, suggesting coordinated arteriolar growth. The sum of AA branch lengths averaged 278 +/- 6 microns. Rat arteriolar renin status, ranging from no renin cells to renin-recruited midafferent arterioles, distributed in a significantly nonrandom fashion within AA pairs, and 52% of the pairs had equal renin status. Hence, AA pairing is a consistent anatomic characteristic of mammalian kidneys and may constitute an optimal vascular design for hemodynamic as well as endocrine interactions.
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PMID:Anatomic pairing of afferent arterioles and renin cell distribution in rat kidneys. 781 Jul

Blockade of angiotensin II AT1 receptors combined with angiotensin I-converting enzyme inhibition might amplify the potency of the renin-angiotensin system blockade. We studied whether chronic and simultaneous administration of enalapril and losartan would result in additive or synergistic effects in the (mREN-2)27 transgenic rat (TGR), the investigated targets being blood pressure, cardiac hypertrophy, renin-angiotensin system blockade achieved, and plasma active renin concentration. In addition, the origin (renal or extrarenal, rat or mouse) of the induced renin release was determined. Adult TGRs were treated orally and daily for 5 to 7 weeks with 1 mg/kg (E1) or 3 mg/kg (E3) enalapril or 1 mg/kg (L1) or 3 mg/kg (L3) losartan, or their combinations (E1L1 and E3L3). At the end of the treatment period, enalapril and losartan exerted dose-dependent and, when combined, additive effects in terms of blood pressure fall and cardiac hypertrophy limitation, and synergistic effects in terms of plasma active renin stimulation and blockade of exogenous angiotensin I pressor effects, with E3L3>E3>L3, E1L1>E1> or =L1, and E1L1=E3>L3). This indicates that in the TGR, (1) the greater the renin-angiotensin system blockade achieved, the greater are the reduction in blood pressure, the limitation of cardiac hypertrophy, and the reactive rise in plasma renin concentration elicited, and (2) the enalapril-losartan combinations are more potent at achieving these goals than any of their constituents individually. In contrast, there was no interaction between the two drugs regarding aldosteronuria reduction. Measurement of plasma renin concentration and renal renin at pH 6.5 and 8.5, ie, the optimal pH values for rat and mouse renin activities, respectively, indicates that in TGRs the counterregulatory process for renin release elicited by enalapril, losartan, or their combination involves primarily rat renin of renal origin, a finding supported further by the observed increase in the rat renal renin hybridization index.
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PMID:Additive effects of enalapril and losartan in (mREN-2)27 transgenic rats. 946 Dec 42

Congenital obstructive nephropathy is a consequence abnormal urinary tract development resulting in renal growth failure and injury manifested by progressive tubular atrophy and interstitial fibrosis. We have studied the renal cellular and physiological response to unilateral ureteral obstruction (UUO) in the neonatal rodent (guinea pig, rat, and mouse). Whereas in the adult, UUO stimulates renal cellular proliferation, UUO in the neonate reduces nephrogenesis, glomerular maturation, and tubular cellular proliferation. This is accompanied by a proportionately greater compensatory growth of the intact opposite kidney in the neonate. Impaired renal growth and tubular atrophy are likely owing at least in part to stimulation of renal tubular apoptosis. This, in turn, may result from a combination of factors, including loss of epithelial cell polarity, a reduction in the oncoprotein bcl-2 and epidermal growth factor (EGF), and increased expression of the fibrogenic cytokine, transforming growth factor-beta1 (TGF-beta1). Infusion of EGF stimulates cellular proliferation, suppresses apoptosis, and reduces tubular atrophy and interstitial fibrosis. TGF-beta1 is regulated by the renin-angiotensin system, which is markedly activated by UUO in the neonate. The functional consequences of obstructive nephropathy in early development are hyperfiltration by remaining nephrons, followed by progressive decrease in glomerular filtration rate that may only develop in later life. Improved management of congenital urinary tract obstruction will depend on a better understanding of the cellular mechanisms, which may lead to specific treatment using gene therapy or modulators of renal growth and development.
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PMID:Pathophysiology of obstructive nephropathy in the newborn. 981 49

With the advances in mouse molecular genetics and physiology during the last decade, the mouse has become the animal model of choice for studying the genetic basis of many diseases. Terms such as "transgenic" and "knockout" have become part of a colloquial language used in most research laboratories that are investigating human diseases. These terms refer to the two most commonly used methods for analyzing the function of a gene in vivo: overexpression (transgenic mouse) and deletion (knockout mouse). Both methods have proved to be extremely useful in establishing the importance of specific genes in genetic disorders, such as hypertension. The choice of genes being investigated in relationship to hypertension was governed by the knowledge of systems regulating vascular and renal physiology. Thus, it is not surprising that most of the focus was given to the renin-angiotensin system (RAS). Apart from the RAS, other systems known to regulate vascular tone and/or electrolyte and fluid homeostasis have also been analyzed using transgenic and knockout approaches. This review briefly summarizes some of the mouse models relevant to renal mechanisms of hypertension and then discusses the future of genetic manipulation in mice for studying the genetics of hypertension.
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PMID:Understanding hypertension through genetic manipulation in mice. 1072 Sep 39

With advances in genetic manipulation and molecular biological and physiological techniques, the mouse has become the animal model of choice for studying the genetic basis of human diseases. The two most commonly used methods for analyzing the function of a gene in vivo, overexpression (transgenic mouse) and deletion (knockout mouse), have been extremely useful in establishing the importance of genes in genetic disorders. The renin-angiotensin system (RAS) is one of the most widely studied systems controlling blood pressure. Although the primary site of Ang-II production is the plasma, all the components of the RAS cascade are expressed in many tissues, including the brain. This review briefly summarizes systemic and tissue-specific transgenic and knockout mouse models of the RAS for determining the role of this system in the regulation of blood pressure and in the pathogenesis of hypertension, with a focus on the RAS in the brain.
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PMID:Angiotensin mutant mice: a focus on the brain renin-angiotensin system. 1235 9

NKCC1 is a widely expressed isoform of the Na-2Cl-K cotransporter that mediates several direct and indirect vascular effects and regulates expression and release of renin. In this study, we used NKCC1-deficient (NKCC1-/-) and wild-type (WT) mice to assess day/night differences of blood pressure (BP), locomotor activity, and renin release and to study the effects of high (8%) or low (0.03%) dietary NaCl intake on BP, activity, and the renin/aldosterone system. On a standard diet, 24-h mean arterial blood pressure (MAP) and heart rate determined by radiotelemetry, and their day/night differences, were not different in NKCC1-/- and WT mice. Spontaneous and wheel-running activities in the active night phase were lower in NKCC1-/- than WT mice. In NKCC1-/- mice on a high-NaCl diet, MAP increased by 10 mmHg in the night without changes in heart rate. In contrast, there was no salt-dependent blood pressure change in WT mice. MAP reductions by hydralazine (1 mg/kg) or isoproterenol (10 microg/mouse) were significantly greater in NKCC1-/- than WT mice. Plasma renin (PRC; ng ANG I.ml(-1).h(-1)) and aldosterone (aldo; pg/ml) concentrations were higher in NKCC1-/- than WT mice (PRC: 3,745+/-377 vs. 1,245+/-364; aldo: 763+/-136 vs. 327+/-98). Hyperreninism and hyperaldosteronism were found in NKCC1-/- mice during both day and night. High Na suppressed PRC and aldosterone in both NKCC1-/- and WT mice, whereas a low-Na diet increased PRC and aldosterone in WT but not NKCC1-/- mice. We conclude that 24-h MAP and MAP circadian rhythms do not differ between NKCC1-/- and WT mice on a standard diet, probably reflecting a balance between anti- and prohypertensive factors, but that blood pressure of NKCC1-/- mice is more sensitive to increases and decreases of Na intake.
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PMID:Salt sensitivity of blood pressure in NKCC1-deficient mice. 1870 22

Hypertension and osteoporosis are two major age-related disorders; however, the underlying molecular mechanism for this comorbidity is not known. The renin-angiotensin system (RAS) plays a central role in the control of blood pressure and has been an important target of antihypertensive drugs. Using a chimeric RAS model of transgenic THM (Tsukuba hypertensive mouse) expressing both the human renin and human angiotensinogen genes, we showed in this study that activation of RAS induces high turnover osteoporosis with accelerated bone resorption. Transgenic mice that express only the human renin gene were normotensive and yet exhibited a low bone mass, suggesting that osteoporosis occurs independently of the development of hypertension per se. Ex vivo cultures showed that angiotensin II (AngII) acted on osteoblasts and not directly on osteoclast precursor cells and increased osteoclastogenesis-supporting cytokines, RANKL and vascular endothelial growth factor (VEGF), thereby stimulating the formation of osteoclasts. Knockdown of AT2 receptor inhibited the AngII activity, whereas silencing of the AT1 receptor paradoxically enhanced it, suggesting a functional interaction between the two AngII receptors on the osteoblastic cell surface. Finally, treatment of THM mice with an ACE inhibitor, enalapril, improved osteoporosis and hypertension, whereas treatment with losartan, an angiotensin receptor blockers specific for AT1, resulted in exacerbation of the low bone mass phenotype. Thus, blocking the synthesis of AngII may be an effective treatment of osteoporosis and hypertension, especially for those afflicted with both conditions.
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PMID:Activation of renin-angiotensin system induces osteoporosis independently of hypertension. 1884 24

Plasma renin activity (PRA) is a well-established biomarker for assessing the efficacy of various antihypertensive agents such as direct renin inhibitors, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors (ACEIs). PRA measurements are obtained through the detection and quantification of angiotensin I (Ang I) produced by the action of renin on its natural substrate angiotensinogen. The most accepted and reproducible method for PRA measurement uses an antibody capture Ang I methodology that employs specific antibodies that recognize and protect Ang I against angiotensinase activities contained in plasma. The amount of Ang I is then quantified by either radioimmunoassay (RIA) or enzyme immunoassay (EIA). In the current report, we describe the optimization of a novel homogeneous immunoassay based on the AlphaScreen technology for the detection and quantification of antibody-captured Ang I using AlphaLISA acceptor beads in buffer and in the plasma of various species (human, rat, and mouse). Ex vivo measurements of renin activity were performed using 10 microl or less of a reaction mixture, and concentrations as low as 1 nM Ang I were quantified. Titration curves obtained for the quantification of Ang I in buffer and plasma gave similar EC(50) values of 5.6 and 14.4 nM, respectively. Both matrices generated an equivalent dynamic range that varies from approximately 1 to 50 nM. Renin inhibitors have been successfully titrated and IC(50) values obtained correlated well with those obtained using EIA methodology (r(2)=0.80). This assay is sensitive, robust, fast, and less tedious than measurements performed using nonhomogeneous EIA. The AlphaLISA methodology is homogeneous, does not require wash steps prior to the addition of reagents, and does not generate radioactive waste.
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PMID:Development of a homogeneous immunoassay for the detection of angiotensin I in plasma using AlphaLISA acceptor beads technology. 1925 5


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