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A Kurtz

Publications and source records attributed to A Kurtz.

At least 37 records · Page 2Linked to original sources
PubMed2001

Differential nNOS gene expression in salt-sensitive and salt-resistant Dahl rats.

BACKGROUND: Several indications exist to suggest that an impaired production of nitric oxide might have a role in the development of salt-sensitive hypertension. OBJECTIVE: To examine whether the gene expression of the nitric oxide synthases (NOS) is altered in the salt-sensitive Dahl rat compared with that in the salt-resistant Dahl rat. DESIGN AND METHODS: The abundance of NOS mRNA was measured by RNase protection assay in different organs of salt-resistant and salt-sensitive Dahl rats. In addition, the zonal expression of NOS genes in the kidney under salt load and salt restriction was determined. RESULTS: The abundance of endothelial NOS mRNA was similar between the salt-resistant and salt-sensitive Dahl rat strains in all organs. Inducible NOS mRNA was not detectable by RNase protection assay in any organ. Neuronal NOS (nNOS) mRNA expression, however, was about 50% lower in brain and kidney of salt-sensitive Dahl rats than in salt-resistant Dahl rats. Within the kidney, nNOS mRNA levels were significantly decreased in salt-sensitive Dahl rats compared with those in salt-resistant Dahl rats, in cortex, outer and inner medulla (50, 40 and 30%, respectively) under all dietary conditions. A comparison of renal nNOS gene expression in Dahl rats with that in salt-insensitive Sprague- Dawley rats revealed that the abundance of renal nNOS was similar in salt-sensitive Dahl and Sprague-Dawley rats, but was increased in salt-resistant Dahl rats relative to that in Sprague-Dawley rats. CONCLUSION: These data suggest that nNOS gene expression is increased in salt-resistant Dahl rats compared with that in salt-sensitive Dahl rats. This increased nNOS expression of the salt-resistant Dahl strain might play a part in compensating for a defect of renal salt excretion in the Dahl strains.

3' Untranslated Regions↗
PubMed2001

Acute upregulation of COX-2 by renal artery stenosis.

This study aimed to characterize the influence of acute renal artery stenosis on cyclooxygenase-2 (COX-2) and renin expression in the juxtaglomerular apparatus. For this purpose, male Sprague-Dawley rats received a left renal artery clip, and COX-2 mRNA, COX-2 immunoreactivity, plasma renin activity, and renin mRNA levels were determined. COX-2 mRNA and COX-2 immunoreactivity in the macula densa region in the clipped kidneys increased as early as 6 h after clipping and reached a maximal expression 1-2 days after clipping. Although values for plasma renin activity were elevated markedly at all time points examined, remaining renin mRNA levels were unchanged after 6 h and then increased to reach a maximum value 1-2 days after clipping. In the contralateral intact kidney, renin mRNA and COX-2 immunoreactivity decreased to approximately 50% of their normal values. To investigate a possible causal relationship between the changes of COX-2 and of renin expression, clipped rats were treated with the COX-2 blocker celecoxib (40 mg. kg(-1). day(-1)). This treatment, however, did not change renin mRNA either in the clipped or in the contralateral intact kidney. Our findings indicate that renal artery stenosis causes ipsilaterally an acute upregulation and contralaterally a downregulation of juxtaglomerular COX-2 expression. The lacking effect of celecoxib on renin gene expression does not support the concept of a direct mediator function of COX-2-derived prostaglandins in the control of renin expression during renal hypoperfusion.

Animals↗
PubMed2001

Functional role of sodium-calcium exchange in the regulation of renal vascular resistance.

Our study aimed to assess a possible functional role of the Na(+)/Ca(2+) exchanger in the regulation of renal vascular resistance (RVR). Therefore, we investigated the effects of an inhibition of the Na(+)/Ca(2+) exchanger either by lowering the extracellular sodium concentration ([Na(+)](e)) or, pharmacologically on RVR, by using isolated perfused rat kidneys. Graded decreases in [Na(+)](e) led to dose-dependent increases in RVR to 4.3-fold (35 mM Na(+)). This vasoconstriction was markedly attenuated by lowering the extracellular calcium concentration, by the L-type calcium channel blocker amlodipine or by the chloride channel blocker niflumic acid. Further lowering of [Na(+)](e) to 7 mM led to an increase in RVR to 7.5-fold. In this setting, amlodipine did not influence the magnitude but did influence the velocity of vasoconstriction. Pharmacological blockade of the Na(+)/Ca(2+) exchanger with KB-R7943, benzamil, or nickel resulted in significant vasoconstriction (RVR 2.5-, 1.8-, and 4.2-fold of control, respectively). Our data suggest a functional role of the Na(+)/Ca(2+) exchanger in the renal vascular bed. In conditions of partial replacement of [Na(+)](e), vasoconstriction is dependent on chloride and L-type calcium channels. A total replacement of [Na(+)](e) leads to a vasoconstriction that is nearly independent of L-type calcium channels. This might be due to an active calcium transport into the cell by the Na(+)/Ca(2+) exchanger.

Amiloride↗
PubMed2001

Differential regulation of cathepsin B and prorenin gene expression in renal juxtaglomerular cells.

Cathepsin B (cathB) is a lysosome cysteine proteinase. It has been suggested to process prorenin to renin in the renin producing juxtaglomerular (JG) cells of the afferent arterioles (AA) of the kidney. Whether cathB expression is regulated similarly to prorenin production is yet unknown. We have measured prorenin and cathB mRNA levels as well as cathB protein levels in renal AA of Sprague-Dawley rats subjected to low (0.02% w/w) salt diet and ramipril treatment (10 mg/kg/day), or to normal (0.6%) or high (4%) salt diet. Prorenin and cathB expression were also analyzed in the JG cell line As4.1. Prorenin mRNA levels in animals on normal (plus ramipril), low or high salt diet correlated as 1:10:0.5, respectively, while cathB mRNA levels correlated as 1:1:0.6, respectively. Treatment of the As4.1 cells with 100 nM phorbol-12-myristate-13-acetate (PMA) for 16 h inhibited prorenin mRNA expression 3-fold relative to the control conditions. CathB mRNA abundance was not different between the PMA treated and the control As4.1 cells. Western analysis of the cathB protein abundance has shown no difference between the rats on normal and low salt diet, and decrease by 50% in the rats on high salt diet. The results of this study suggest that prorenin and cathB gene expression in renal JG cells are differentially regulated.

Angiotensin II↗
PubMed2001

Downregulation of angiotensin II type 1 receptors during sepsis.

Our study aimed to characterize the mechanisms underlying the attenuated cardiovascular responsiveness toward the renin-angiotensin system during sepsis. For this purpose, we determined the effects of experimental Gram-negative and Gram-positive sepsis in rats. We found that sepsis led to a ubiquitous upregulation of NO synthase isoform II expression and to pronounced hypotension. Despite increased plasma renin activity and plasma angiotensin (Ang) II levels, plasma aldosterone concentrations were normal, and the blood pressure response to exogenous Ang II was markedly diminished in septic rats. Mimicking the fall of blood pressure during sepsis by short-term infusion of the NO donor sodium nitroprusside in normal rats did not alter their blood pressure response to exogenous Ang II. Therefore, we considered the possibility of an altered expression of Ang II receptors during sepsis. It turned out that Ang II type 1 receptor expression was markedly downregulated in all organs of septic rats. Further in vitro studies with rat renal mesangial cells showed that NO and a combination of proinflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma) downregulated Ang II type 1 receptor expression in a synergistic fashion. In summary, our data suggest that sepsis causes a systemic downregulation of Ang II type 1 receptors that is likely mediated by proinflammatory cytokines and NO. We suggest that this downregulation of Ang II type 1 receptors is the main reason for the attenuated responsiveness of blood pressure and of aldosterone formation to Ang II and, therefore, contributes to the characteristic septic shock.

Adrenal Glands↗
PubMed2001

Application of three-dimensional ultrasonography in the evaluation of the fetal heart.

The objectives of this study were to determine whether three-dimensional ultrasonography can provide more cardiac views than two-dimensional ultrasonography and to develop a standard technique. Eighteen women, 16 to 26 weeks' gestation, were scanned with two-dimensional ultrasonography for 10 minutes or less to obtain fetal heart views. Three-dimensional ultrasonography was used (< or =10 minutes) to obtain up to 4 acquisitions of the fetal heart: 4-chamber view, left parasagittal, transverse, and longitudinal nonstandard. Views were later extracted from saved volume data, comparing the yields of two- and three-dimensional ultrasonography. The 4-chamber view was obtained in 15 (93%) of 16 cases on both two- and three-dimensional ultrasonography. On two-dimensional ultrasonography, the left outflow tract was obtained in 68% of the cases; on three-dimensional ultrasonography, the left outflow tract was obtained in 46% from the 4-chamber view acquisition and in 100% from the left parasagittal acquisition. On two-dimensional ultrasonography, the right outflow tract was obtained in 68% of the cases; on three-dimensional ultrasonography, the right outflow tract was obtained in 86% from the 4-chamber view acquisition and in 71% from the left parasagittal acquisition. Aortic and ductal arches were obtained in 12% and 18%, respectively, on two-dimensional ultrasonography. On three-dimensional ultrasonography the aortic and ductal arches were obtained in 66% and 86%, respectively, from the 4-chamber view acquisition and in 57% and 71%, respectively, from the left parasagittal acquisition. Three-dimensional ultrasonography permitted a greater number of cardiac views to be extracted from volume data than did two-dimensional ultrasonography.

Echocardiography, Three-Dimensional↗
PubMed2000

Breast cancer growth inhibition by delivery of the MDGI-derived peptide P108.

Mammary derived growth inhibitor (MDGI) is a member of the family of cytoplasmic fatty acid binding proteins (FABPs), which bind hydrophobic ligands such as fatty acids, retinoids, eicosanoids and prostaglandines. MDGI and an 11 amino acid MDGI-derived conserved C-terminal peptide (P108) inhibits growth of normal mammary epithelial cells in tissue and organ culture, but fails to inhibit proliferation of many breast cancer cell lines in vitro. Here, the effects of peptide P108 on tumor growth of MCF-7, MDA-MB468 and MDA-MB231 human breast cancer cell lines in nude mice were tested. To deliver P108 into tumors, a novel peptide production system was applied for expression and secretion of small bioactive peptides in mammalian cells. Functional differentiation was observed in MCF-7 and MDA-MB468 cells upon P108 expression. In addition, EGF-dependent colony formation in soft agar by MDA-MB468 cells was inhibited by secreted P108. Tumor growth in athymic nude mice was suppressed in all three cell lines tested. Furthermore, P108 expressed by MCF-7/P108 cells caused paracrine tumor growth inhibition of MDA-MB231 cells. These results indicate that breast cancer inhibition by P108 is independent of binding to hydrophobic ligands and is perhaps mediated by interference with EGF-dependent signaling pathways.

Amino Acid Sequence↗
PubMed2000

Role of potassium channels in the control of renin secretion from isolated perfused rat kidneys.

This study aimed to assess the relevance of specific potassium channels, such as inwardly or outwardly rectifying and calcium-regulated potassium channels, to the control of renin secretion. For this purpose we examined the effects of the K+ channel blockers 4-aminopyridine (1 mmol/l), barium (100 micromol/l), tetraethylammonium (2 mmol/l) and apamin (200 nmol/l) on basal renin secretion, on renin secretion stimulated by isoproterenol (10 nmol/l) and on the inhibition of renin secretion by angiotensin II (100-300 pmol/l) in the isolated rat kidney perfused at constant pressure. Whilst all four K+ channel blockers increased renal vascular resistance, only 4-aminopyridine and barium attenuated isoproterenol-stimulated renin secretion in an additive fashion and augmented the inhibitory effect of angiotensin II. These effects of K+ channel blockers were not changed by the L-type calcium channel blocker amlodipine (5 pmol/l), indicating that their effects on renin secretion are not due to voltage-operated calcium influx. Our data, moreover, suggest that potassium efflux from renal juxtaglomerular cells is not important for the inhibitory action of angiotensin II on renin secretion. As a consequence it appears that the membrane potential of renal juxtaglomerular cells per se is relevant to renin secretion such that membrane depolarization inhibits the exocytosis of renin whilst hyperpolarization favors renin secretion. By their activity, potassium channels can contribute to membrane hyperpolarization and thus facilitate renin secretion.

4-Aminopyridine↗
PubMed2000

Cyclooxygenase 2 and neuronal nitric oxide synthase expression in the renal cortex are not interdependent in states of salt deficiency.

Neuronal nitric oxide synthase (nNOS) and cyclooxygenase-2 (COX-2) expression in the kidney are localized to the cortical thick ascending limb of the loop of Henle (cTALH), including the macula region, and increase after salt restriction. Because of the similar localization and regulation of nNOS and COX-2 expression, we have examined whether there is a functional interrelationship between the expression of the two enzymes. Male Sprague Dawley rats were fed for 1 week either a low-salt diet (0.02% w/w) which produced moderate increases of nNOS and COX-2 expression, or low salt combined with the angiotensin I converting enzyme inhibitor ramipril (10 mg/kg per day), which produced strong increases of renocortical nNOS and COX-2 expressions. To inhibit nNOS or COX-2 activities, animals received in addition N(G)-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg per day) or rofecoxib (10 mg/kg per day) for 1 week, respectively. L-NAME treatment did not change COX-2 expression and conversely rofecoxib treatment did not change nNOS expression in the kidney cortex under any experimental conditions. L-NAME but not rofecoxib attenuated renin mRNA levels. Rofecoxib markedly reduced renal prostanoid excretion. These findings suggest that under these conditions the control of nNOS and COX-2 gene expression in the macula densa regions of the kidney cortex are not dependent on each other.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Endogenous nitric oxide attenuates erythropoietin gene expression in vivo.

This study aimed to investigate the role of endogenous nitric oxide (NO) in erythropoietin (EPO) gene expression in mice in vivo. For this purpose EPO mRNA was semiquantitated by ribonuclease protection assay in livers and kidneys of three groups of mice: wild-type (wt), endothelial NO-synthase (NOS) knockout mice (eNOS-/-), and wt treated with the NOS inhibitor N(G)-nitro-L-arginine methyl ester (50 mg x kg(-1) x day(-1)) for 4 days (wt+L-NAME). EPO gene expression was stimulated by normobaric hypoxia (8% O2) or by 0.1% carbon monoxide (CO) inhalation for 4 h each, or by intraperitoneal injection of 60 mg/kg cobaltous chloride (CoCl2) for 6 h. Renal EPO mRNA in wt increased 12-, 40-, and 13-fold over normoxic levels in response to hypoxia, CO and CoCl2 respectively. EPO mRNA was detectable in the livers only after CO exposure. Renal and hepatic EPO gene expression in wt+L-NAME appeared moderately increased relative to wt with a maximal 2.5-fold enhancement after CO exposure. EPO mRNA levels in eNOS-/- mirrored those of wt+L-NAME, but the effects were less prominent. Our data suggest that endogenous NO attenuates EPO gene expression in mice. This effect is dependent on the rate of EPO gene induction.

Animals↗
PubMed2000

Regulation of renin gene expression in kidneys of eNOS- and nNOS-deficient mice.

Our study aimed to assess the roles of nitric oxide derived from endothelium NO-synthase (eNOS) and macula densa neuronal NO-synthase (nNOS) in the regulation of renal renin expression. For this purpose renin mRNA levels and renin content were determined in kidneys of wild-type (wt), nNOS-deficient (nNOS-/-), and eNOS-deficient (eNOS-/-) mice, in which the renin system was suppressed by feeding a high-salt diet (NaCl 4%), or was stimulated by feeding a low-salt (NaCl 0.02%) diet together with the converting-enzyme inhibitor ramipril (10 mg kg(-1) day(-1)). In all mouse strains, renin mRNA levels were inversely related to the rate of sodium intake. In eNOS-/- mice renin mRNA levels and renal renin content were 50% lower than in wt mice at each level of salt intake, whilst in nNOS-/- mice renin expression was not different from wt controls. Administration of the general NO-synthase inhibitor nitro-L-arginine methyl ester (L-NAME, 50 mg kg(-1) day(-1)) to mice kept on the low-salt/ramipril regimen caused a decrease of renal renin mRNA levels in wt and nNOS-/- mice, but not in eNOS-/- mice. These observations suggest that neither eNOS nor nNOS is essential for up- or downregulation of renin expression. eNOS-derived NO appears to enhance renin expression, whereas nNOS-derived NO does not.

Animals↗
PubMed2000

Mode of nitric oxide action on the renal vasculature.

Our study aimed to characterize the essential cellular pathways along which nitric oxide (NO) exerts its well-known vasodilatatory properties in the kidney. Using the isolated perfused rat kidney model we examined the roles of potassium channels, cGMP-protein kinase activity and cAMP-phosphodiesterases (PDE) in the effect of NO on renovascular resistance. We found that neither potassium channel activity nor G-kinase activity was essential for the vasodilatatory effect of NO. The effect of NO, however, was essentially mimicked by pharmacological inhibition of PDE-3, which is a cGMP-inhibitable PDE. As PDE-3 is strongly expressed in renal preglomerular vessels and NO stimulates cGMP formation in renal vessels, it appears likely that inhibition of cAMP degradation and consequently the cAMP pathway are crucially involved in mediating the effects of NO on renal vascular resistance.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Overexpression of chloride channel CLC-K2 mRNA in the renal medulla of Dahl salt-sensitive rats.

OBJECTIVE: The present study aimed to characterize the influence of salt intake on the gene expression of the kidney specific chloride channels CLC-K1 and CLC-K2 in the kidneys of salt-resistant and salt-sensitive Dahl rats. DESIGN: For this purpose Dahl salt-resistant (Dahl-R) and Dahl salt-sensitive rats (Dahl-S) were fed a low (0.02%), normal (0.6%) or high (4%) salt diet for 19 days and CLC-K1 and -K2 mRNA expression was semiquantitated in cortex, outer and inner medulla. METHODS: Kidneys were macroscopically dissected, total RNA was isolated according to the guanidinium-thiocyanate-phenol-chloroform method and messenger RNAs for the kidney specific chloride channels CLC-K1 and CLC-K2 were measured by ribonuclease protection assay. RESULTS: Systolic blood pressure in high salt-treated Dahl-S rats increased to 204 +/- 5 mmHg versus 150 +/- 7 mmHg in Dahl-S controls. Dahl R and low salt Dahl-S rats showed no increase in blood pressure. For CLC-K1 mRNA we found an order of abundance inner medulla >> outer medulla >> cortex. There was no difference in mRNA abundance between Dahl-R and -S, nor any effect of the rate of salt intake on CLC-K1 mRNA abundance in the different kidney zones. CLC-K2 mRNA expression in cortex and outer medulla was similar between Dahl-R and -S rats. In the inner medulla, however, CLC-K2 mRNA was 1.7-fold higher in Dahl-S than in Dahl-R rats. In the cortex we found no influence of salt intake on CLC-K2 mRNA. In outer and inner medulla of Dahl-R rats and Dahl-S rats high salt diet led to a marked downregulation of CLC-K2 mRNA expression. Consequently, CLC-K2 gene expression in the inner medulla was 2.2-fold higher in Dahl-S than in Dahl-R rats in states of high salt diet. CONCLUSION: Given that the CLC-K2 chloride channel in the outer and inner medulla contributes to salt reabsorption, our findings would suggest that Dahl-S rats have an increased medullary salt reabsorption. This may contribute to the inability of these animals to excrete an increased salt load at a normal renal perfusion pressure leading to the development of hypertension.

Animals↗
PubMed2000

Tissue hypoxygenation activates the adrenomedullin system in vivo.

Our study aimed to investigate the influence of tissue hypo-oxygenation on the adrenomedullin (ADM) system in vivo. For this purpose, male Sprague-Dawley rats were exposed to normobaric hypoxia (8% oxygen) or to functional anemia [0.1% carbon monoxide (CO)] or to cobalt chloride (60 mg/kg) for 6 h. Messenger RNA levels for ADM and its receptor (ADM-R) were assessed in diverse organs by RNase protection assay. Additionally, ADM protein concentrations in these organs, as in plasma, were determined by a RIA. We found that ADM mRNA abundance increased in response to hypoxia and to CO inhalation up to 15-fold in all organs examined. Similarly, ADM-R mRNA abundance increased during hypoxia and CO inhalation in all organs examined with exception of the liver. The effects of hypoxia and of CO inhalation on ADM and ADM-R mRNAs were mimicked by injection of cobaltous chloride. Hypoxia also significantly increased ADM protein content in all organs, and plasma levels of ADM rose twofold in response to hypoxia and CO inhalation. These findings indicate that tissue hypoxia leads to a widespread activation of the ADM system, which comprises a parallel stimulation of ADM and ADM receptor mRNA as enhanced ADM protein synthesis and secretion. The ADM system may, therefore, play a significant role in the physiological response to tissue hypoxia. It appears that ADM and ADM-R belong to the family of classic oxygen-regulated genes, which are activated by a decrease of the pericellular oxygen tension through the same intracellular signaling cascade.

Administration, Inhalation↗
PubMed2000

Store-operated calcium influx inhibits renin secretion.

On the basis of evidence that changes in the extracellular concentration of calcium effectively modulate renin secretion from renal juxtaglomerular cells, our study aimed to determine the effect of calcium influx activated by depletion of intracellular calcium stores on renin secretion. For this purpose we characterized the effects of the endoplasmatic Ca(2+)-ATPase inhibitors thapsigargin (300 nM) and cyclopiazonic acid (20 microM) on renin secretion from isolated perfused rat kidneys. We found that Ca(2+)-ATPase inhibition caused a potent inhibition of basal renin secretion as well as renin secretion activated by isoproterenol, bumetanide, and by a fall in the renal perfusion pressure. The inhibitory effect of Ca(2+)-ATPase inhibition on renin secretion was reversed within seconds by lowering of the extracellular calcium concentration into the submicromolar range but was not affected by lanthanum, gadolinium, flufenamic acid, or amlodipine. These data suggest that calcium influx triggered by release of calcium from internal stores is a powerful mechanism to inhibit renin secretion from juxtaglomerular cells. The store-triggered calcium influx pathway in juxtaglomerular cells is apparently not sensitive to classic blockers of the capacitative calcium entry pathway.

Animals↗
PubMed1999

Nitric oxide/cAMP interactions in the control of rat renal vascular resistance.

This study aimed to characterize the interaction between nitric oxide (NO)- and cAMP-related pathways in the control of renal blood flow. Using the isolated perfused rat kidney model, we determined the effects of inhibition of NO formation by Nomega-nitro-L-arginine methyl ester (L-NAME; 1 mmol/L) and of NO administration by sodium nitroprusside (SNP, 10 micromol/L) on renal vascular resistance under conditions of elevated vascular cAMP levels. cAMP levels were increased either by adenylate cyclase activation via isoproterenol or by inhibition of cAMP phosphodiesterases (PDEs) 1, 3, and 4. We found that L-NAME markedly increased vascular resistance and that this effect was completely reversed by SNP. Both isoproterenol and inhibitors of the cAMP PDEs lowered basal vascular resistance. In the presence of isoproterenol (3 nmol/L) and inhibitors of PDE-1 [8-methoxymethyl-l-methyl-3-(2-methylpropyl)-xanthine; 8-MM-IBMX, 20 micromol/L] and PDE-4 (rolipram, 20 micromol/L), L-NAME again substantially increased vascular resistance, and this effect of L-NAME was completely reversed by SNP. In the presence of the PDE-3 inhibitors milrinone (20 micromol/L) and trequinsin (200 nmol/L), however, both L-NAME and SNP failed to exert any additional effects. Because PDE-3 is a cGMP-inhibited cAMP PDE and because the vasodilatory effect of SNP was abrogated by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (20 micromol/L), our findings are compatible with the idea that an action of NO on PDE-3 could account for the vasodilatory properties of NO on the renal vasculature. Moreover, our findings suggest that PDE-3 activity is an important determinant of renal vascular resistance.

Adenylyl Cyclases↗