534 results on '"Schnermann, Jurgen"'
Search Results
202. Inhibition of nNOS expression in the macula densa by COX-2-derived prostaglandin E2.
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Paliege, Alex, Mizel, Diane, Medina, Carmen, Pasumarthy, Anita, Huang, Yuning G., Bachmann, Sebastian, Briggs, Josephine P., Schnermann, Jurgen B., and Yang, Tianxin
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CYCLOOXYGENASE 2 ,NITRIC oxide ,JUXTAGLOMERULAR apparatus ,REVERSE transcriptase ,POLYMERASE chain reaction ,IMMUNOHISTOCHEMISTRY ,STAINS & staining (Microscopy) - Abstract
It is well established that cyclooxygenase-2 (COX-2) and the neuronal form of nitric oxide synthase (nNOS) are coexpressed in macula densa cells and that the expression of both enzymes is stimulated in a number of high-renin states. To further explore the role of nNOS and COX-2 in renin secretion, we determined plasma renin activity in mice deficient in nNOS or COX-2. Plasma renin activity was significantly reduced in nNOS -/- mice on a mixed genetic background and in COX-2 -/- mice on either BALB/c or C57/BL6 congenic backgrounds. In additional studies, we accumulated evidence to show an inhibitory influence of PGE
2 on nNOS expression. In a cultured macula densa cell line, PGE2 significantly reduced nNOS mRNA expression, as quantified by real-time RT-PCR. In COX-2 -/- mice, nNOS mRNA expression in the kidney, determined by real-time RT-PCR, was upregulated throughout the postnatal periods, ranging from postnatal day (PND) 3 to PND 60. The induction of nNOS protein expression and NOS activity in COX-2 -/- mice was localized to macula densa cells using immunohistochemistry and NADPH-diaphorase staining methods, respectively. Therefore, these findings reveal that the absence of either COX-2 or nNOS is associated with suppressed renin secretion. Furthermore, the inhibitory effect of PGE2 on nNOS mRNA expression indicates a novel interaction between NO and prostaglandin-mediated pathways of renin regulation. [ABSTRACT FROM AUTHOR]- Published
- 2004
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203. A[sub 1] adenosine receptor knockout mice exhibit increased renal injury folowing ischemia and reperfusion.
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Lee, H. Thomas, Hua Xu, Nasr, Samih H., Schnermann, Jurgen, and Emala, Charles W.
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ACUTE kidney failure ,INFLAMMATION ,ADENOSINES ,ISCHEMIA ,REPERFUSION injury - Abstract
Controversy exists regarding the effect of Al adenosine receptor (AR) activation in the kidney during ischemia and reperfusion (I/R) injury. We sought to further characterize the role of A
1 ARs in modulating renal function after I/R renal injury using both pharmacological and gene deletion approaches in mice. A1 AR knockout mice (A1 KO) or their wild-type littermate controls (A1 WT) were subjected to 30 min of renal ischemia. Some A1 WT mice were subjected to 30 min of renal ischemia with or without pretreatment with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) or 2-chrolo-cyclopentyladenosine (CCPA), selective A1 AR antagonist and agonist, respectively. Plasma creatinine and renal histology were compared 24 h after renal injury. A1 KO mice exhibited significantly higher creatinines and worsened renal histology compared with A1 WT controls following renal I/R injury. A1 WT mice pretreated with the A1 AR antagonist or agonist demonstrated significantly worsened or improved renal function, respectively, after I/R injury. In addition, A1 WT mice pretreated with DPCPX or CCPA showed significantly increased or reduced markers of renal inflammation, respectively (renal myeloperoxidase activity, renal tubular neutrophil infiltration, ICAM-1, TNF-α, and IL-β mRNA expression), while demonstrating no differences in indicators of apoptosis. In conclusion, we demonstrate that endogenous or exogenous preischemic activation of A1 ARs protects against renal I/R injury in vivo via mechanisms leading to decreased necrosis and inflammation. [ABSTRACT FROM AUTHOR]- Published
- 2004
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204. Regulation of cyclooxygenase-2 expression in renal medulla by tonicity in vivo and in vitro.
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Tianxin Yang and Schnermann, Jurgen B.
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CYCLOOXYGENASES , *KIDNEY physiology - Abstract
Studies the regulation of cyclooxygenase-2 (COX-2) expression in renal medulla by tonicity in vivo and in vitro. Tissue distribution of COX-1 and COX-2 expression; Effects of sodium chloride on COX-2 promoter activity in transfected MDCK cells; Influence of genistein on osmotic stimulation of COX-2 expression.
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- 1999
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205. Absence of tubuloglomerular feedback responses in AT1A receptor-deficient mice.
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Schnermann, Jurgen B. and Traynor, Timothy
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ANGIOTENSINS , *KIDNEY tubules - Abstract
Assesses tubuloglomerular feedback responses in mice that carries a null mutation in the angiotensin II AT1A receptor gene. Dose-response relationship between mean arterial blood pressure and single bolus injections of angiotensin II; Feasibility of utilizing complex micropuncture approaches to assess glomerular and tubular function in genetically altered mice.
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- 1997
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206. Effects of barium ions on tubuloglomerular feedback.
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Schnermann, Jurgen
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POTASSIUM channels , *KIDNEY glomerulus , *PHYSIOLOGY - Abstract
Presents a study to evaluate the effect of potassium channel blockade with barium on tubuloglomerular (TGF) responses. Changes in luminal sodium chloride concentration; Vasoconstrictor effect of barium; Sodium-chloride-potassium cotransport; Macula densa.
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- 1995
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207. Regulation of cyclooxygenase expression in the kidney by...
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Yang, Tianxin, Singh, Inderjit, Pham, Hang, Daqing Sun, Smart, Ann, Schnermann, Jurgen B., and Briggs, Josephine P.
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CYCLOOXYGENASES ,KIDNEYS ,PHYSIOLOGICAL effects of salts ,CYTOLOGY ,REACTIVITY (Chemistry) - Abstract
Examines the effect of altering dietary salt intake on renal cyclooxygenase (COX) expression. Distribution of COX-1 and COX-2 expression in kidney regions; Localization of COX-1 and COX-2 along the nephron; Expression of COX-1 and COX-2 in cultured renal cells.
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- 1998
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208. Distribution of mineralocorticoid and glucocorticoid receptor mRNA along the nephron.
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TODD-TURLA, ARYN M., SCHNERMANN, JURGEN, FEJES-TOTH, GEZA, NARAY-FEJES-TÓTH, ANIKO, SMART, ANN, KILLEN, PAUL D., and BRIGGS, JOSIE P.
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- 1993
209. Vasomotor effects of purinergic agonists in isolated rabbit afferent arterioles.
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WEIHPRECHT, HORST, LORENZ, JOHN N., BRIGGS, JOSIE P., and SCHNERMANN, JURGEN
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- 1992
210. Restoration of tubuloglomerular feedback in volume-expanded rats by angiotensin II.
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SCHNERMANN, JURGEN and BRIGGS, JOSIE P.
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- 1990
211. Characterization of the macula densa stimulus for renin secretion.
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LORENZ, JOHN N., WEIHPRECHT, HORST, SCHNERMANN, JURGEN, SKØTT, OLE, and BRIGGS, JOSIE P.
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- 1990
212. Effect of dopamine on the tubuloglomerular feedback mechanism.
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SCHNERMANN, JURGEN, TODD, KARYN M., and BRIGGS, JOSEPHINE P.
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- 1990
213. Inhibition of tubuloglomerular feedback during adenosine1 receptor blockade.
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SCHNERMANN, JURGEN, WEIHPRECHT, HORST, and BRIGGS, JOSIE P.
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- 1990
214. Interaction between loop of Henle flow and arterial pressure as determinants of glomerular pressure.
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SCHNERMANN, JURGEN and BRIGGS, JOSEPHINE P.
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- 1989
215. Effect of adenosine analogues on tubuloglomerular feedback responses.
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SCHNERMANN, JURGEN
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- 1988
216. In situ studies of distal convoluted tubule in rat. II. K secretion.
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SCHNERMANN, JURGEN, STEIPE, BORIS, and BRIGGS, JOSEPHINE P.
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- 1987
217. Opposing effects of captopril and aprotinin on tubuloglomerular feedback responses.
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SCHNERMANN, JURGEN, BRIGGS, JOSEPHINE P., SCHUBERT, GISELA, and MARIN-GREZ, MARCOS
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- 1984
218. Defective proximal tubular fluid reaborption in transgenic aquaporin-1 null mice.
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Schnermann, Jurgen, Chou, Chung-Lin, Ma, Tonghui, Traynor, Timothy, Knepper, Mark A., and Verkman, A.S.
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MICE physiology ,BODY fluids ,WATER in the body ,ABSORPTION - Abstract
Presents a study on the role of aquaporin-1 (AQP1) in proximal tubule water transport and fluid reabsorption in mice. Methodology used in the study; Measurement of transepithelial osmotic water permeability and fluid reabsorption under in vitro conditions; Major pathway for osmotically driven water transport; Conclusion on additional aquaporin-type water channels.
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- 1998
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219. Macula Densa Control of Renin Secretion and Glomerular Vascular Tone: Evidence for Common Cellular Mechanisms.
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Briggs, Josephine P. and Schnermann, Jurgen
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- 1986
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220. Juxtaglomerular cell complex in the regulation of renal salt excretion.
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Schnermann, Jurgen
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CELL physiology ,JUXTAGLOMERULAR apparatus ,EXCRETION - Abstract
Examines cellular processes in the juxtaglomerular apparatus (JGA) during the regulation of renal salt excretion. Description of JGA; Functions of the JGA; Mechanisms of transport-related changes in JGA function.
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- 1998
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221. Abnormal autoregulation and tubuloglomerular feedback in prediabetic and diabetic OLETF rats
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Hashimoto, Seiji, Yamada, Kanji, Kawata, Tetsuya, Mochizuki, Toshio, Schnermann, Jurgen, and Koike, Takao
- Abstract
The mechanisms underlying the development and prevention of diabetic nephropathy are still not fully understood. In the present study in the Otsuka Long-Evans Tokushima Fatty (OLETF) model of type 2 diabetic rats, we investigated whether renal hemodynamic abnormalities exist and whether they precede the onset of diabetes. Using OLETF rats in both prediabetic and diabetic stages, we assessed autoregulatory responses of total renal blood flow (RBF) and of superficial (SBF) and deep renal cortical (DBF) blood flow to stepwise reductions of renal perfusion pressure (RPP) induced by a manual clamp on the abdominal aorta. During clamp-induced reductions of RPP by 10 or 20 mmHg, RBF fell significantly more in OLETF rats than in lean control [Long-Evans Tokushima Otsuka (LETO)] rats. Whereas SBF showed no significant changes in either OLETF rats or LETO rats during mild clamping, DBF decreased significantly more in OLETF rats than LETO rats. Reduced autoregulatory efficiency in OLETF rats was observed in both prediabetic and diabetic stages. Micropuncture studies showed that tubuloglomerular feedback (TGF) responses of stop flow pressure are reduced in prediabetic (−7.3 vs. −25.7%) as well as in diabetic OLETF rats compared with LETO control rats (−4.4 vs. −18.8%). Renal corticotomy was performed to measure glomerular capillary pressure (Pgc) directly. Pgcof deep cortical glomeruli was higher than superficial glomerular Pgcin both strains of rats, but the difference was especially pronounced in OLETF rats (deep 78 ± 2 vs. superficial 57 ± 4 mmHg). This study demonstrates reduced autoregulatory adjustments and impaired TGF efficiency in prediabetic OLETF rats. Thus abnormal RBF regulation precedes the onset of diabetes and is especially pronounced in the deep cortical region.
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- 2009
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222. Isoforms of renal Na-K-2Cl cotransporter NKCC2: expression and functional significance
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Castrop, Hayo and Schnermann, Jurgen
- Abstract
The renal Na-K-2Cl cotransporter (NKCC2, BSC1) is selectively expressed in the apical membrane of cells of the thick ascending limb of the loop of Henle (TAL) and macula densa. NKCC2-dependent salt transport constitutes the major apical entry pathway for transepithelial salt reabsorption in the TAL. Although NKCC2 is encoded by a single gene (Slc12a1), differential splicing of the NKCC2 pre-mRNA results in the formation of several alternate transcripts. Thus three full-length splice isoforms of NKCC2 differ in their variable exon 4, resulting in transcripts for NKCC2B, NKCC2A, and NKCC2F. In addition to full-length isoforms, variants with truncated COOH-terminal ends have been described. The various splice isoforms of NKCC2 differ in their localization along the TAL and in their transport characteristics. Data in the literature are reviewed to assess the principles of NKCC2 differential splicing, the localization of NKCC2 splice isoforms along the TAL in various species, and the functional characteristics of the splice isoforms. In addition, we discuss the functional significance of NKCC2 isoforms for TAL salt retrieval and for the specific salt sensor function of macula densa cells based on studies using isoform-specific NKCC2-knockout mice. We suggest that different NKCC2 splice variants cooperate in salt retrieval along the TAL and that the coexpression of two splice variants (NKCC2B and NKCC2A) in the macula densa cells facilitates efficient salt sensing over wide ranges of fluctuating salt concentrations.
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- 2008
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223. Salt sensitivity of blood pressure in NKCC1-deficient mice
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Kim, Soo Mi, Eisner, Christoph, Faulhaber-Walter, Robert, Mizel, Diane, Wall, Susan M., Briggs, Josephine P., and Schnermann, Jurgen
- Abstract
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 μg/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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- 2008
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224. Tubuloglomerular feedback and renin secretion in NTPDase1/CD39-deficient mice
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Oppermann, Mona, Friedman, David J., Faulhaber-Walter, Robert, Mizel, Diane, Castrop, Hayo, Enjyoji, Keiichi, Robson, Simon C., and Schnermann, Jurgen
- Abstract
Studies in mice with null mutations of adenosine 1 receptor or ecto-5′-nucleotidase genes suggest a critical role of adenosine and its precursor 5′-AMP in tubulovascular signaling. To assess whether the source of juxtaglomerular nucleotides can be traced back to ATP dephosphorylation, experiments were performed in mice with a deficiency in NTPDase1/CD39, an ecto-ATPase catalyzing the formation of AMP from ATP and ADP. Urine osmolarity and glomerular filtration rate (GFR) were indistinguishable between NTPDase1/CD39−/−and wild-type (WT) mice. Maximum tubuloglomerular feedback (TGF) responses, as determined by proximal tubular stop flow pressure measurements, were reduced in NTPDase1/CD39−/−mice compared with controls (4.2 ± 0.9 vs. 10.5 ± 1.2 mmHg, respectively; P= 0.0002). Residual TGF responses gradually diminished after repeated changes in tubular perfusion flow averaging 2.9 ± 0.9 (on response) and 3.5 ± 1.1 (off response) mmHg after the second and 2.2 ± 0.5 (on response) and 1.5 ± 0.8 (off response) mmHg after the third challenge, whereas no fading of TGF responsiveness was observed in WT mice. Macula densa-dependent and pressure-dependent inhibition of renin secretion, as assessed by acute salt loading and phenylephrine injection, respectively, were intact in NTPDase1/CD39-deficient mice. In summary, NTPDase1/CD39-deficient mice showed a markedly compromised TGF regulation of GFR. These data support the concept of an extracellular dephosphorylation cascade during tubular-vascular signal transmission in the juxtaglomerular apparatus that is initiated by a regulated release of ATP from macula densa cells and results in adenosine-mediated afferent arteriole constriction.
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- 2008
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225. Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by furosemide in mice
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Oppermann, Mona, Hansen, Pernille B., Castrop, Hayo, and Schnermann, Jurgen
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Loop diuretics like furosemide have been shown to cause renal vasodilatation in dogs and humans, an effect thought to result from both a direct vascular dilator effect and from inhibition of tubuloglomerular feedback. In isolated perfused afferent arterioles preconstricted with angiotensin II or NG-nitro-l-arginine methyl ester, furosemide caused a dose-dependent increase of vascular diameter, but it was without effect in vessels from NKCC1−/− mice suggesting that inhibition of NKCC1 mediates dilatation in afferent arterioles. In the intact kidney, however, furosemide (2 mg/kg iv) caused a 50.5 ± 3% reduction of total renal blood flow (RBF) and a 27% reduction of superficial blood flow (SBF) accompanied by a marked and immediate increase of tubular pressure and volume. At 10 mg/kg, furosemide reduced RBF by 60.4 ± 2%. Similarly, NKCC1−/− mice responded to furosemide with a 45.4% decrease of RBF and a 29% decrease of SBF. Decreases in RBF and SBF and increases of tubular pressure by furosemide were ameliorated by renal decapsulation. In addition, pretreatment with candesartan (2 mg/kg) or indomethacin (5 mg/kg) attenuated the reduction of RBF and peak urine flows caused by furosemide. Our data indicate that furosemide, despite its direct vasodilator potential in isolated afferent arterioles, causes a marked increase in flow resistance of the vascular bed of the intact mouse kidney. We suggest that generation of angiotensin II and/or a vasoconstrictor prostaglandin combined with compression of peritubular capillaries by the expanding tubular compartment are responsible for the reduction of RBF in vivo.
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- 2007
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226. Regulation of renin in mice with Cre recombinase-mediated deletion of G protein Gsα in juxtaglomerular cells
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Chen, Limeng, Kim, Soo Mi, Oppermann, Mona, Faulhaber-Walter, Robert, Huang, Yuning, Mizel, Diane, Chen, Min, Lopez, Maria Luisa Sequeira, Weinstein, Lee S., Gomez, R. Ariel, Briggs, Josie P., and Schnermann, Jurgen
- Abstract
By crossing mice with expression of Cre recombinase under control of the endogenous renin promoter (Sequeira Lopez ML, Pentz ES, Nomasa T, Smithies O, Gomez RA. Dev Cell6: 719–728, 2004) with mice in which exon 1 of the Gnasgene was flanked by loxP sites (Chen M, Gavrilova O, Liu J, Xie T, Deng C, Nguyen AT, Nackers LM, Lorenzo J, Shen L, Weinstein LS. Proc Natl Acad Sci USA), we generated animals with preferential and nearly complete excision of Gsα in juxtaglomerular granular (JG) cells. Compared with wild-type animals, mice with conditional Gsα deficiency had markedly reduced basal levels of renin expression and very low plasma renin concentrations. Furthermore, the acute release responses to furosemide, hydralazine, and isoproterenol were virtually abolished. Consistent with a state of primary renin depletion, Gsα-deficient mice had reduced arterial blood pressure, reduced levels of aldosterone, and a low glomerular filtration rate. Renin content and renin secretion of JG cells in primary culture were drastically reduced, and the stimulatory response to the addition of PGE2or isoproterenol was eliminated. Unexpectedly, Gsα recombination was also observed in the renal medulla, and this was associated with a vasopressin-resistant concentrating defect. Our study shows that Cre recombinase under control of the renin promoter can be used for the excision of floxed targets from JG cells. We conclude that Gsα-mediated signal transduction is essential and nonredundant in the control of renin synthesis and release.
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- 2007
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227. Low plasma renin and reduced renin secretory responses to acute stimuli in conscious COX-2-deficient mice
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Kim, Soo Mi, Chen, Limeng, Mizel, Diane, Huang, Yuning G., Briggs, Josie P., and Schnermann, Jurgen
- Abstract
In the current experiments, we determined the response of plasma renin concentration (PRC) to acute intraperitoneal administration of furosemide (40 mg/kg), hydralazine (2 mg/kg), isoproterenol (10 mg/kg), candesartan (50 μg), or quinaprilate (50 μg) in conscious wild-type (WT) and cyclooxygenase (COX)-2−/− mice on three different genetic backgrounds (mixed, C57BL/6, 129J). PRC was measured in plasma obtained by tail vein puncture. Basal PRC was significantly lower in COX-2−/− than WT mice independent of genetic background (51, 10, and 17% of WT in mixed, 129J, and C57BL/6). All five acute interventions caused significant increases of PRC in both COX-2+/+ and −/− mice, but the response was consistently less in COX-2-deficient mice (e.g., ΔPRC in ng ANG I·ml−1·h−1caused by furosemide, isoproterenol, hydralazine, quinaprilate, or candesartan 4,699 ± 544, 3,534 ± 957, 2,522 ± 369, 9,453 ± 1,705, 66,455 ± 21,938 in 129J WT, and 201 ± 78, 869 ± 275, 140 ± 71, 902 ± 304, 2,660 ± 954 in 129J COX-2−/−). A low-NaCl diet and enalapril for 1 wk caused a 14-fold elevation of PRC in COX-2−/− mice and was associated with a greatly increased PRC response to acute furosemide (ΔPRC 201 ± 78 before and 15,984 ± 2,397 after low Na/enalapril). As measured by radiotelemetry, blood pressure and heart rate responses to furosemide, hydralazine, isoproterenol, candesartan, or quinaprilate were not different between COX-2 genotypes. In conclusion, chronic absence of COX-2 reduces renin expression, release, and PRC and is associated with a reduced ability to alter PRC during acute stimulation regardless of the nature of the stimulus. COX-2 activity does not appear to be a mandatory and specific requirement for furosemide-stimulated renin secretion.
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- 2007
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228. Nitric oxide stimulates COX-2 expression in cultured collecting duct cells through MAP kinases and superoxide but not cGMP
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Yang, Tianxin, Zhang, Aihua, Pasumarthy, Anita, Zhang, Lihong, Warnock, Zachary, and Schnermann, Jurgen B.
- Abstract
Collecting ducts are a major site of renal production and action of both prostaglandins and nitric oxide. Experiments were undertaken to examine whether nitric oxide regulates cyclooxygenase (COX)-2 expression and PGE2release in cultured collecting duct cells. In mIMCD-K2 cells, sodium nitroprusside (SNP) in the 50- to 800-μM range induced a marked dose- and time-dependent increase in COX-2 protein levels, determined by immunoblotting, and the induction was detectable at 4 h. This was preceded by induction of COX-2 mRNA as determined by real-time-RT-PCR. The COX-2 induction was accompanied by a significant rise in PGE2release as determined by enzyme immunoassay. S-nitroso-N-acetylpenicillamine (SNAP) had a similar stimulatory effect on COX-2 expression and PGE2release. 8-bromo-cGMP (200 μM) had no effect on COX-2 expression. The SNP-stimulated COX-2 expression was not affected by the guanylyl cyclase inhibitor methylene blue or the protein kinase G inhibitor KT-5823 (2.0 μM). In contrast, the SNP-stimulated COX-2 expression was significantly reduced by either the Erk1/2 inhibitor PD-98059 or the P38 inhibitor SB-203580 and was abolished by combination of the two kinase inhibitors. The stimulation was also significantly blocked by the SOD mimetic tempol. Thus we conclude that NO stimulates COX-2 expression in collecting duct cells through mechanisms involving MAP kinase and superoxide, but not cGMP.
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- 2006
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229. Adenosine as a mediator of macula densa-dependent inhibition of renin secretion
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Kim, Soo Mi, Mizel, Diane, Huang, Yuning G., Briggs, Josie P., and Schnermann, Jurgen
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Adenosine acting through A1 adenosine receptors (A1AR) has been shown previously to be required for the vasoconstriction elicited by high luminal NaCl concentrations at the macula densa (MD). The present experiments were performed to investigate a possible role of A1AR in MD control of renin secretion in conscious wild-type (WT) and A1AR-deficient mice. The intravenous injection of NaCl (5% body wt) reduced plasma renin concentration (PRC; ng ANG I·ml–1·h–1) from 1,479 ± 129 to 711 ± 77 (P < 0.0001; n = 18) in WT mice but did not significantly change PRC in A1AR–/– mice (1,352 ± 168 during control vs. 1,744 ± 294 following NaCl; P = 0.19; n = 17). NaCl injections also caused a significant reduction in PRC in β1/β2-adrenergic receptor–/– mice (298 ± 47 vs. 183 ± 42; P = 0.03; n = 6). Injections of isotonic NaHCO3 (5% body wt) elicited significant increases in PRC in both WT and A1AR–/– mice. NaCl as well as NaHCO3 injections were accompanied by transient increases in blood pressure, heart rate, and activity that were similar in WT and A1AR–/– mice. The increase in PRC caused by an intraperitoneal injection of furosemide (40 mg/kg) was comparable in WT and A1AR–/– mice, and it was accompanied by similar transient increases in blood pressure, heart rate, and activity. Similarly, the stimulation of PRC caused by hydralazine was the same in WT and A1AR–/– mice. We conclude that the inhibition of renin secretion in response to an increase in NaCl at the MD requires A1AR and therefore appears to be adenosine dependent, whereas the stimulation of renin secretion during reductions in MD NaCl transport or arterial pressure does not require functional A1AR.
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- 2006
230. Influence of genetic background and gender on hypertension and renal failure in COX-2-deficient mice
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Yang, Tianxin, Huang, Yuning G., Ye, Wenling, Hansen, Pernille, Schnermann, Jurgen B., and Briggs, Josephine P.
- Abstract
The present study was undertaken to determine whether the severity of renal failure or hypertension in homozygous cyclooxygenase (COX)-2-deficient (COX-2−/−) mice affected by genetic background or gender. COX-2 deletion was introduced into three congenic genetic backgrounds, 129/Sv (129/COX-2−/−), C57/BL6 (C57/COX-2−/−), and BALB/c (BALB/COX-2−/−), by backcrossing the original mixed-background knockout mice with the respective inbred strains for 9 or 10 generations. Evaluation of the severity of hypertension and renal failure was performed in knockout and wild-type mice at the age of 2.5–3.5 mo. Blood pressure measured by tail-cuff plethysmography was significantly elevated in the male 129/COX-2−/− mice (165.8 ± 9.2 vs. 116 ± 5.1 mmHg, P< 0.05), and to a much lesser extent in the female 129/COX-2−/− mice (127.4 ± 3.3 vs. 102.4 ± 3.3), whereas it was unchanged in the C57- or BALB/COX-2−/− mice regardless of gender. Urinary excretion of albumin, determined by EIA, was remarkably increased in the 129/COX-2−/− (16.4 ± 4.1 vs. 0.16 ± 0.043 mg albumin/mg creatinine, P< 0.001), and to a lesser extent in the male C57/COX-2−/− mice (0.595 ± 0.416 vs. 0.068 ± 0.019). Albumin excretion was not elevated in the male BALB/COX-2−/− or in female COX-2−/− mice on any of the three genetic backgrounds. Histological analysis showed abundant protein casts, dilated tubules, and infiltration of inflammatory cells in the male 129/COX-2−/− mice, but not in COX-2−/− mice in other strains or gender. However, the presence of small glomeruli in the nephrogenic zone was observed in all strains of COX-2 knockout mice, regardless of genetic background and gender. Therefore, we conclude that the severity of hypertension and renal failure in COX-2-deficient mice is influenced by genetic background and gender, whereas the incomplete maturation of outer cortical nephrons appears to be independent of genetic background effects.
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- 2005
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231. Requirement of intact adenosine A1 receptors for the diuretic and natriuretic action of the methylxanthines theophylline and caffeine.
- Author
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Rieg, Timo, Steigele, Hannah, Schnermann, Jurgen, Richter, Kerstin, Osswald, Hartmut, and Vallon, Volker
- Abstract
Although the diuretic and natriuretic effects of the methylxanthines caffeine and theophylline are well established, the mechanisms responsible for these effects are unclear and may be related to inhibition of phosphodiesterases and/or antagonism of adenosine receptors. With regard to the latter, pharmacological blockade of A1 receptors can induce diuresis and natriuresis by inhibition of proximal tubular reabsorption. To elucidate the role of the A1 receptor in renal actions of methylxanthines, experiments were performed in A1 receptor knockout (A1R-/-) and littermate wild-type (A1R+/+) mice. Urinary excretion was determined in awake mice in metabolic cages over 3 h in response to theophylline (as theophylline2/ethylenediamine, 45 mg/kg), caffeine (45 mg/kg), or vehicle (0.9 ml/30 g b.wt. of 0.85% NaCl) given by oral gavage. Theophylline and caffeine elicited a diuresis and natriuresis (in absolute terms and related to urinary creatinine excretion) in A1R+/+ but not in A1R-/- mice. In a second series, the renal effect of intravenous application of theophylline (30 mg/kg) was determined in clearance experiments under anesthesia. This study revealed that the blunted diuretic and natriuretic effect of theophylline in A1R-/- mice was not due to different responses in blood pressure or glomerular filtration rate. The data indicate that an intact A1 receptor is necessary for caffeine- and theophylline-induced inhibition of renal reabsorption causing diuresis and natriuresis. This is consistent with the assumption that A1 receptor blockade mediates these effects.
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- 2005
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232. Inhibition of nNOS expression in the macula densa by COX-2-derived prostaglandin E2
- Author
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Paliege, Alex, Mizel, Diane, Medina, Carmen, Pasumarthy, Anita, Huang, Yuning G., Bachmann, Sebastian, Briggs, Josephine P., Schnermann, Jurgen B., and Yang, Tianxin
- Abstract
It is well established that cyclooxygenase-2 (COX-2) and the neuronal form of nitric oxide synthase (nNOS) are coexpressed in macula densa cells and that the expression of both enzymes is stimulated in a number of high-renin states. To further explore the role of nNOS and COX-2 in renin secretion, we determined plasma renin activity in mice deficient in nNOS or COX-2. Plasma renin activity was significantly reduced in nNOS −/− mice on a mixed genetic background and in COX-2 −/− mice on either BALB/c or C57/BL6 congenic backgrounds. In additional studies, we accumulated evidence to show an inhibitory influence of PGE2on nNOS expression. In a cultured macula densa cell line, PGE2significantly reduced nNOS mRNA expression, as quantified by real-time RT-PCR. In COX-2 −/− mice, nNOS mRNA expression in the kidney, determined by real-time RT-PCR, was upregulated throughout the postnatal periods, ranging from postnatal day(PND) 3to PND 60. The induction of nNOS protein expression and NOS activity in COX-2 −/− mice was localized to macula densa cells using immunohistochemistry and NADPH-diaphorase staining methods, respectively. Therefore, these findings reveal that the absence of either COX-2 or nNOS is associated with suppressed renin secretion. Furthermore, the inhibitory effect of PGE2on nNOS mRNA expression indicates a novel interaction between NO and prostaglandin-mediated pathways of renin regulation.
- Published
- 2004
- Full Text
- View/download PDF
233. Permissive role of nitric oxide in macula densa control of renin secretion
- Author
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Castrop, Hayo, Schweda, Frank, Mizel, Diane, Huang, Yuning, Briggs, Josie, Kurtz, Armin, and Schnermann, Jurgen
- Abstract
Experiments were performed in neuronal (nNOS)- and endothelial nitric oxide synthase (eNOS)-deficient mice to study the role of nitric oxide (NO) in macula densa control of renin secretion in vivo and in the isolated, perfused mouse kidney. Acute and chronic administration of loop diuretics was used as a method to stimulate macula densa-mediated renin secretion. Increases in plasma renin concentration (PRC) in response to a 3-day infusion of bumetanide (50 mg·kg-1·day-1) or an acute injection of furosemide (50 mg/kg ip) were not markedly altered in nNOS-/- mice. Responses to furosemide were also maintained in eNOS-/- mice, but the administration of Nω-nitro-l-arginine methyl ester (l-NAME) markedly attenuated the PRC response to furosemide in these mice. In the isolated kidney preparation, bumetanide caused similar relative increases in renin secretion in kidneys of wild-type, nNOS-/-, and eNOS-/- mice. Bumetanide only marginally increased renin secretion in l-NAME-treated kidneys, but the bumetanide effect was normalized by S-nitroso-N-acetyl-penicillamine. Basal PRC was significantly reduced in male nNOS-/- mice compared with nNOS+/+ (189 ± 28 vs. 355 ± 57 ng ANG I ·ml-1·h-1; P= 0.017). There was no significant difference in PRC between eNOS+/+ and eNOS-/- mice. Basal renin secretion rates in perfused kidneys isolated from nNOS-/- or eNOS-/- mice were markedly reduced compared with wild-type controls. Our data suggest that NO generated by macula densa nNOS does not play a specific mediator role in macula densa-dependent renin secretion. However, NO independent of its exact source permits the macula densa pathway of renin secretion to function normally.
- Published
- 2004
- Full Text
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234. Vasoconstrictor and vasodilator effects of adenosine in the kidney
- Author
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Hansen, Pernille B. and Schnermann, Jurgen
- Abstract
Adenosine is an ATP breakdown product that in most vessels causes vasodilatation and that contributes to the metabolic control of organ perfusion, i.e., to the match between oxygen demand and oxygen delivery. In the renal vasculature, in contrast, adenosine can produce vasoconstriction, a response that has been suggested to be an organ-specific version of metabolic control designed to restrict organ perfusion when transport work increases. However, the vasoconstriction elicited by an intravenous infusion of adenosine is only short lasting, being replaced within 1–2 min by vasodilatation. It appears that the steady-state response to the increase of plasma adenosine levels above normal resulting from the infusion is global renal vasorelaxation that is the result of A2AR activation in most parts of the renal vasculature, including larger renal arteries, juxtamedullary afferent arterioles, efferent arterioles, and medullary vessels. A2AR-mediated vasorelaxation is probably facilitated by endothelial receptors that cause the release of nitric oxide and other endothelial relaxing factors. In contrast, isolated perfused afferent arterioles of superficial and midcortical nephrons of rabbit and mouse, especially in their most distal segment at the entrance to the glomerulus, respond to adenosine with persistent vasoconstriction, indicating predominant or exclusive expression of A1AR. A1AR in afferent arterioles are selectively activated from the interstitial aspect of the vessel. This property can dissociate A1AR activation from changes in vascular adenosine concentration, a characteristic that is ideally suited for the role of renal adenosine as a paracrine factor in the control of glomerular function.
- Published
- 2003
- Full Text
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235. Regulation of cyclooxygenase-2 expression in renal medulla by tonicity in vivo and in vitro
- Author
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Yang, Tianxin, Schnermann, Jurgen B., and Briggs, Josephine P.
- Abstract
Renal medullary prostaglandins are believed to exert an important functional role in antagonizing vasopressin effects in dehydration. Studies were undertaken to determine the effect of hyperosmolality on cyclooxygenase (COX) isoform expression in the renal medulla. COX-1 and COX-2 mRNA and protein levels were determined by RT-PCR or Western blotting in Sprague-Dawley rats on varying water intakes, in Brattleboro rats and in Long-Evans controls. Over a wide range of urinary tonicity, COX-2 expression correlated closely with urine osmolality levels (R= 0.872). COX-1 levels did not vary. Immunolocalization showed that the stimulation of COX-2 expression by dehydration occurred predominantly in the collecting duct. Hypertonicity caused by addition of NaCl produced a dose- and time-dependent stimulation of COX-2 expression in mIMCD-K2 cells as well as in MDCK cells. COX-1 was unaffected. In the same cell lines, mannitol, sucrose, and raffinose also had a stimulatory effect. The tonicity-stimulated COX-2 expression in mIMCD-K2 cells was almost completely blocked by a tyrosine kinase inhibitor, genistein at 100 μM. In MDCK cells transfected with a 2.7-kb COX-2 promoter andlacZ reporter construct, NaCl induced a twofold increase in β-galactosidase activity. Using mIMCD-K2 cells, hypertonic NaCl (600 mosmol/kgH2O for 24 h) induced a 33-fold increase in PGE2release determined by enzyme immunoassay, an effect completely blocked by 3 μM indomethacin or the COX-2-specific blockerN-(2-cyclohexy-4-nitrophenyl)methanesulfonamide (NS-398). We conclude that in inner medulla, COX-2 but not COX-1 is upregulated by hyperosmolality.
- Published
- 1999
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236. Differential regulation of COX-2 expression in the kidney by lipopolysaccharide: role of CD14
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Yang, Tianxin, Sun, Daqing, Huang, Yuning G., Smart, Ann, Briggs, Josephine P., and Schnermann, Jurgen B.
- Abstract
Induction of the inducible cyclooxygenase isoform COX-2 is likely to be an important mechanism for increased prostaglandin production in renal inflammation. We examined the effect of lipopolysaccharide (LPS) on regional renal COX-2 expression in the rat. In the inner medulla, LPS injection (4 mg/kg ip) induced a twofold and 2.5-fold increase in the levels of COX-2 mRNA and COX-2 protein, respectively. In contrast, COX-2 expression in the renal cortex was not significantly altered. COX-2 promoter transgenic mice were created using the 2.7-kb flanking region of the rat COX-2 gene. In these animals, LPS injection induced reporter gene expression predominately in the inner medulla. The LPS receptor CD14, usually regarded as a monocyte/macrophage-specific marker, was found to be abundantly expressed in the inner medulla and in dissected inner medullary collecting duct (IMCD) cells, suggesting that it may mediate medullary COX-2 induction. CD14 was present only at low levels in cortex and cortical segments, including glomeruli. In cultured cells, it was abundant in mouse IMCD (mIMCD-K2) cells and renal medullary interstitial cells, but largely undetectable in mesangial cells and M1 cells, a cell line derived from mouse cortical collecting ducts. In the mIMCD-K2 cell line, LPS significantly induced COX-2 mRNA expression, with concomitant induction of CD14. LPS-stimulated COX-2 expression was reduced by the addition of an anti-CD14 monoclonal antibody to the culture medium. These results demonstrate that LPS selectively stimulates COX-2 expression in the renal inner medulla through a CD14-dependent mechanism.
- Published
- 1999
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237. Expression of peroxisomal proliferator-activated receptors and retinoid X receptors in the kidney
- Author
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Yang, Tianxin, Michele, Daniel E., Park, John, Smart, Ann M., Lin, Zhiwu, Brosius, Frank C., Schnermann, Jurgen B., and Briggs, Josephine P.
- Abstract
The discovery that 15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2) is a ligand for the γ-isoform of peroxisome proliferator-activated receptor (PPAR) suggests nuclear signaling by prostaglandins. Studies were undertaken to determine the nephron localization of PPAR isoforms and their heterodimer partners, retinoid X receptors (RXR), and to evaluate the function of this system in the kidney. PPARα mRNA, determined by RT-PCR, was found predominately in cortex and further localized to proximal convoluted tubule (PCT); PPARγ was abundant in renal inner medulla, localized to inner medullary collecting duct (IMCD) and renal medullary interstitial cells (RMIC); PPARβ, the ubiquitous form of PPAR, was abundant in all nephron segments examined. RXRα was localized to PCT and IMCD, whereas RXRβ was expressed in almost all nephron segments examined. mRNA expression of acyl-CoA synthase (ACS), a known PPAR target gene, was stimulated in renal cortex of rats fed with fenofibrate, but the expression was not significantly altered in either cortex or inner medulla of rats fed with troglitazone. In cultured RMIC cells, both troglitazone and 15d-PGJ2significantly inhibited cell proliferation and dramatically altered cell shape by induction of cell process formation. We conclude that PPAR and RXR isoforms are expressed in a nephron segment-specific manner, suggesting distinct functions, with PPARα being involved in energy metabolism through regulating ACS in PCT and with PPARγ being involved in modulating RMIC growth and differentiation.
- Published
- 1999
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238. Cyclooxygenase-2 is expressed in bladder during fetal development and stimulated by outlet obstruction
- Author
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Park, John M., Yang, Tianxin, Arend, Lois J., Smart, Ann M., Schnermann, Jurgen B., and Briggs, Josephine P.
- Abstract
Studies were undertaken to assess expression of inducible cyclooxygenase (COX)-2 in bladder during fetal development and COX-1 and COX-2 expression after outlet obstruction. Bladder tissue or bladder progenitor tissue was harvested from CD-1 murine embryos at embryonic days 11.5(E11.5),E14.5,E17.5,E20.5(newborn), and from adult. Bladder obstruction was created in adult female mice by ligating the urethra, and bladders were harvested after 3–24 h of obstruction. Gene expression was assessed by semiquantitative reverse transcription-polymerase chain reaction and Western blotting. COX-2 was highly expressed at the early stages of bladder development and declined progressively throughout gestation. In adult bladder, both COX-1 and COX-2 were detectable at low levels under basal conditions. An ∼30-fold increase in COX-2 mRNA was seen after 24 h of obstruction. In contrast, COX-1 did not change with obstruction. COX-2 mRNA levels peaked at 6 h of obstruction. In regional bladder-distention models, COX-2 induction was confined to the area of distention. Bladder outlet obstruction stimulates COX-2 expression dramatically, reactivating a gene that is highly expressed during fetal development.
- Published
- 1997
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239. Macula Densa Control of Renin Secretion and Glomerular Vascular Tone: Evidence for Common Cellular Mechanisms
- Author
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Briggs, Josephine P., primary and Schnermann, Jurgen, additional
- Published
- 1986
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240. The Tubuloglomerular Feedback Mechanism: Functional and Biochemical Aspects
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Briggs, Josephine P., primary and Schnermann, Jurgen, additional
- Published
- 1987
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241. Kidney Hormones. Volume III.J. W. Fisher
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Schnermann, Jurgen, primary
- Published
- 1987
- Full Text
- View/download PDF
242. Tubuloglomerular feedback and glomerular morphology in Goldblatt hypertensive rats on varying protein diets
- Author
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Schnermann, Jurgen, primary, Gokel, Michael, additional, Weber, Peter C., additional, Schubert, Gisela, additional, and Briggs, Josephine P., additional
- Published
- 1986
- Full Text
- View/download PDF
243. Kidney Hormones. Volume III. J. W. Fisher
- Author
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Schnermann, Jurgen
- Published
- 1987
244. The expanding role of aldosterone in the regulation of body Na content.
- Author
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Schnermann, Jurgen
- Subjects
- *
ALDOSTERONE , *SODIUM , *ABSORPTION (Physiology) , *RENIN , *BILE ducts , *BLOOD plasma - Abstract
Examines the expanding role of aldosterone in the regulation of body sodium content. Role of aldosterone as a stimulator of sodium reabsorption in the collecting duct; Effect of low sodium intake or a loss of blood on volume depletion and plasma aldosterone levels; Factor affecting the augmentation of the release of renin through the macula densa mechanism.
- Published
- 2003
- Full Text
- View/download PDF
245. Dense core vesicle proteins IA-2 and IA-2beta - novel regulators of renin secretion and circadian blood pressure rhythms.
- Author
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Soo Mi Kim, Hiroki Hirai, Tao Cai, Limeng Chen, Faulhaber-Walter, Robert, Yuning Huang, Mizel, Diane, Briggs, Josie P., Notkins, Abner L., and Schnermann, Jurgen
- Subjects
PROTEINS ,RENIN ,CIRCADIAN rhythms ,BLOOD pressure ,JUXTAGLOMERULAR apparatus ,LABORATORY mice - Abstract
The dense core vesicle proteins IA-2 and IA-2β have recently been found in renal afferent arterioles in a location consistent with expression in juxtaglomerular cells. To identify a possible role of IAs in renin secretion we compared plasma renin concentration (PRC, ng AngI/ml hr) as index of renin release in wild type (WT) and IA-2/IA-213 double knockout mice (DKO; Kubosaki A. et al. 2005). PRC was lower in DKO than WT (596 ± 81 vs. 1454 ± 122; n=16 vs. n=10; p<.0001). Renin mRNA in DKO was 38.0 ± 5.8 % of WT (p<0.001, n=9). On a high NaCl diet (8%), PRC decreased in both genotypes remaining lower in DKO than WT (276 ± 59 vs. 676 ± 128; p<0.01). Furosemide increased PRC to a lesser extent in DKO than WT (to 5536 ± 620 vs. 9416 ± 956). GFR, plasma aldosterone, and urine osmolarity did not differ between DKO and WT. 24 h mean arterial blood pressure (MAP) measured by telemetry was not different in WT and DKO (106 ± 2 vs. 111 ± 3 mm Hg), but the day-night difference in MAP (1.8 ± 1 mm Hg vs. 12 ± 1.4 mm Hg; p<.0001) or heart rate was abolished in DKO. Locomotor activity of DKO in the active phase was only 25.5% of WT. In summary: 1) Basal renin synthesis and release is dependent upon IA-2 /IA-2β, 2) modulation of renin release by salt intake is maintained in IA DKO, and 3) circadian MAP and locomotor variations are absent in IA DKO. We conclude: IAs are positive regulators of renin secretion, synthesis and circadian blood pressure and activity rhythms. [ABSTRACT FROM AUTHOR]
- Published
- 2007
246. Telemetric blood pressure studies in NKCC1-deficient mice.
- Author
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Soo Mi Kim, Yuning Huang, Faulhaber-Walter, Robert, Mizel, Diane, Wall, Susan M., Briggs, Josie P., and Schnermann, Jurgen
- Subjects
BLOOD pressure measurement ,SODIUM in the body ,RENIN-angiotensin system ,VASODILATION ,ARTERIES ,RENIN ,LABORATORY mice - Abstract
Blood pressure measurements by tail-cuff have shown reduced levels in NKCC1-deficient mice (NKCC1-/-). By radiotelemetry 24h mean arterial blood pressure (MAP) was not different in NKCC1-/- and WT mice (108 ± 2 vs. 110 ± 2 mm Hg; n=19 vs. n=7). MAP was not altered by either 1 week low (0.03%) or high Na intake (8%) in WT mice. In NKCC1-/- MAP decreased in the day time during low Na and increased by about 10 mm Hg at night time during high Na. MAP reductions in response to hydralazine (1 mg/kg), isoproterenol (10 µg/mouse), candesartan (50 µg/mouse) and quinaprilate (50 µg/mouse) were consistently and significantly greater in NKCC1-/- than WT mice. PRC (ng Ang I/ml hr) and aldosterone (pg/ml) were higher in NKCC1-/- than WT (PRC: 5566 ± 825 vs.1458 ± 165; aldo: 974 ± 100 vs. 456 ± 108). High Na suppressed PRC and aldosterone in both NKCC1-/- and WT (PRC: 1202 ± 181 vs. 287 ± 96; aldo: 178 ± 25 vs.162 ± 56) while a low Na diet increased PRC and aldosterone in WT but not NKCC1-/-. In summary: 1) 24h MAP is the same in NKCC1-/- and WT on standard diets, 2) MAP of NKCC1-/- mice is more sensitive to increases and decreases of Na intake than MAP of WT, 3) plasma renin and aldosterone are elevated in NKCC1-/- mice. We conclude that NKCC1 stabilizes MAP in response to changes in Na intake and peripheral vasodilation, and that this may be related to a more responsive renin system. [ABSTRACT FROM AUTHOR]
- Published
- 2007
247. letters to the editor.
- Author
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Malvin, Richard L., Schnermann, Jurgen B., Churchill, Paul C., and Bidani, Anil K.
- Published
- 1992
248. Inhibition of nNOS expression in the macula densa by COX-2-derived prostaglandin E(2).
- Author
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Alex, Paliege, Diane, Mizel, Carmen, Medina, Anita, Pasumarthy, G, Huang Yuning, Sebastian, Bachmann, P, Briggs Josephine, B, Schnermann Jurgen, and Tianxin, Yang
- Abstract
It is well established that cyclooxygenase-2 (COX-2) and the neuronal form of nitric oxide synthase (nNOS) are coexpressed in macula densa cells and that the expression of both enzymes is stimulated in a number of high-renin states. To further explore the role of nNOS and COX-2 in renin secretion, we determined plasma renin activity in mice deficient in nNOS or COX-2. Plasma renin activity was significantly reduced in nNOS -/- mice on a mixed genetic background and in COX-2 -/- mice on either BALB/c or C57/BL6 congenic backgrounds. In additional studies, we accumulated evidence to show an inhibitory influence of PGE(2) on nNOS expression. In a cultured macula densa cell line, PGE(2) significantly reduced nNOS mRNA expression, as quantified by real-time RT-PCR. In COX-2 -/- mice, nNOS mRNA expression in the kidney, determined by real-time RT-PCR, was upregulated throughout the postnatal periods, ranging from postnatal day (PND) 3 to PND 60. The induction of nNOS protein expression and NOS activity in COX-2 -/- mice was localized to macula densa cells using immunohistochemistry and NADPH-diaphorase staining methods, respectively. Therefore, these findings reveal that the absence of either COX-2 or nNOS is associated with suppressed renin secretion. Furthermore, the inhibitory effect of PGE(2) on nNOS mRNA expression indicates a novel interaction between NO and prostaglandin-mediated pathways of renin regulation.
- Published
- 2004
249. Convergence of major physiological stimuli for renin release on the Gs-alpha/cyclic adenosine monophosphate signaling pathway.
- Author
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Kim, Soo, Briggs, Josephine, and Schnermann, Jurgen
- Subjects
- *
RENIN , *CYCLIC adenylic acid , *CELLULAR signal transduction , *BARORECEPTORS , *GENE expression , *CYCLOOXYGENASES , *PHOSPHODIESTERASES , *ACE inhibitors , *NITRIC-oxide synthases - Abstract
Control of the renin system by physiological mechanisms such as the baroreceptor or the macula densa (MD) is characterized by asymmetry in that the capacity for renin secretion and expression to increase is much larger than the magnitude of the inhibitory response. The large stimulatory reserve of the renin-angiotensin system may be one of the causes for the remarkable salt-conserving power of the mammalian kidney. Physiological stimulation of renin secretion and expression relies on the activation of regulatory pathways that converge on the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway. Mice with selective Gs-alpha (Gsα) deficiency in juxtaglomerular granular cells show a marked reduction of basal renin secretion, and an almost complete unresponsiveness of renin release to furosemide, hydralazine, or isoproterenol. Cyclooxygenase-2 generating prostaglandin E (PGE) and prostacyclin (PGI) in MD and thick ascending limb cells is one of the main effector systems utilizing Gsα-coupled receptors to stimulate the renin-angiotensin system. In addition, β-adrenergic receptors are critical for the expression of high basal levels of renin and for its release response to lowering blood pressure or MD sodium chloride concentration. Nitric oxide generated by nitric oxide synthases in the MD and in endothelial cells enhances cAMP-dependent signaling by stabilizing cAMP through cyclic guanosine monophosphate-dependent inhibition of phosphodiesterase 3. The stimulation of renin secretion by drugs that inhibit angiotensin II formation or action results from the convergent activation of cAMP probably through indirect augmentation of the activity of PGE and PGI receptors, β-adrenergic receptors, and nitric oxide. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
250. Defective renal autoregulation in the chronic bile duct ligation model of liver failure.
- Author
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Maoka, Tomchika, Kawata, Tetsuya, Koike, Takao, Mochizuki, Toshio, Schnermann, Jurgen, and Hashimoto, Seiji
- Subjects
- *
CIRRHOSIS of the liver , *LIVER failure , *BILIRUBIN , *BILE ducts , *BLOOD flow - Abstract
Background: Cirrhosis of the liver is often associated with an impairment of renal function that is usually not associated with consistent structural abnormalities of the renal parenchyma, but is thought to be the functional consequence of arterial underfilling and reduced arterial blood pressure.Method: We have used the cirrhosis model of chronic bile duct ligation (BDL) to assess the response of renal blood flow to a change of blood pressure. We have measured renal haemodynamics in BDL rats.Result: Three weeks after BDL, rats showed elevated levels of total bilirubin, AST, and ALT as well as reduced arterial blood pressure. Creatinine clearance was significantly reduced, and plasma creatinine and urea nitrogen were elevated. Renal blood flow at baseline blood pressure was significantly lower in the BDL group than in the sham group. Clamp-induced reductions of renal perfusion pressure caused significantly greater changes of renal blood flow in BDL than control rats. The autoregulatory index over a comparable blood pressure range averaged 0.28 ± 0.35 in control rats and 1.26 ± 0.6 in BDL rats (p = 0.0004) indicating impairment of renal autoregulation in liver cirrhosis.Conclusion: Tubuloglomerular feedback (TGF) responses were significantly attenuated in BDL rats, especially in the subnormal flow range. Impairment of renal blood flow autoregulation, to some extent mediated by reduced TGF-mediated vasodilatation, may contribute to the renal vascular constrictor state in liver cirrhosis by preventing the full dilatory response to the blood pressure reduction. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
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