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A Kurtz

Publications and source records attributed to A Kurtz.

At least 109 records · Page 6Linked to original sources
PubMed1996

Blockade of nitric oxide formation inhibits the stimulation of the renin system by a low salt intake.

This study aimed to investigate the possible involvement of endothelial autacoids such as nitric oxide or prostaglandins in the well-known stimulatory effect of a low salt intake on renin secretion and renin gene expression in the kidney. To this end, plasma renin activity (PRA) and kidney renin mRNA levels were determined in male Sprague-Dawley rats fed either a normal (0.6% w/w) or a low (0.03%) NaCl diet for 10 days. To inhibit nitric oxide formation, the animals received L-nitro-argininemethylester (L-NAME, 40 mg/ kg twice a day), to inhibit prostaglandin formation the animals received meclofenamate (8 mg/kg twice a day) during the last 2 days. In animals fed a normal salt diet, L-NAME decreased PRA from 6.5 to 4.9 ng angiotensin I x h(-1) x ml(-1) and decreased renin mRNA levels by about 15%. Meclofenamate did not change PRA or renin mRNA in animals fed on normal salt diet. In vehicle-treated animals fed a low salt diet, PRA increased from 6.5 to 20.2 ng ANGI x h(-1) x ml(-1) and renin mRNA levels increased by 100%. Meclofenamate treatment did not alter these changes of PRA and renin mRNA during the intake of a low salt diet. In animals treated with L-NAME, PRA increased to only 7.2 ng ANGI x h(-1) x ml(-1) and renin mRNA increased by 20%. These findings indicate that inhibition of nitric oxide formation but not of prostaglandin formation substantially attenuates the stimulatory effect of a low salt intake on the renin system, suggesting that nitric oxide is required for this process.

Animals↗
PubMed1996

Coordinate changes of renin and brain-type nitric-oxide-synthase (b-NOS) mRNA levels in rat kidneys.

In our study we have examined the mRNA levels of nitric-oxide-(NO-)synthases in rat kidneys during states of stimulated and reduced renin gene expression, to find out whether renal mRNA levels of NO-synthases are correlated with the activity of the renin system. Stimulation of the renin system was achieved by unilateral renal artery clipping (2-kidney/1-clip rats), treatment with the angiotensin II (ANG II) antagonist losartan (40 mg/kg), application of furosemide (12 mg x kg-1 x day-1) and a low-sodium diet (0.02% w/w Na+), which increased renin mRNA levels to 464%, 495%, 309% and 219% of those of control animals, respectively. Inhibition of the renin system was achieved in the nonclipped (contralateral) kidneys of 2-kidney/1-clip rats and in the kidneys of rats which were fed a high-sodium diet (4% w/w Na+); in both cases renin mRNA levels decreased to about 50% of the control values. First screening of the gene expression of brain-type NO-synthase (b-NOS), endothelial NOS (e-NOS) and inducible NOS (i-NOS) during all these alterations of the renin system was done using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. Results from such noncompetitive PCR experiments indicated that only b-NOS mRNA levels change concordantly with the levels of renin. These changes in b-NOS mRNA levels were checked by the more reliable method of RNase protection assay. Results of the RNase protection assay proved that the renal levels of b-NOS mRNA were significantly increased by about 50% after a low-sodium diet and hypoperfusion of the kidney. Given a stimulatory role of endothelium-derived relaxing factor (EDRF)/NO on the renin system our findings may provide the first evidence that increases of renal levels of b-NOS mRNA and, as a consequence, of renal EDRF/NO formation could be important mediators of the well-known effect of salt intake and hypoperfusion on the renin system.

Angiotensin II↗
PubMed1996

Differential effects of kinase inhibitors on erythropoietin and vascular endothelial growth factor gene expression in rat hepatocytes.

This study sought to investigate whether a common protein kinase activity is involved in the sequence of events by which oxygen controls the expression of the genes for erythropoietin (EPO) and for vascular endothelial growth factor (VEGF) in rat hepatocytes. To this end we examined the influence of the non-specific kinase inhibitor staurosporine and of the tyrosine kinase inhibitor genistein on EPO and VEGF mRNA levels in primary cultures of rat hepatocytes kept at either high (20% O2) or low (1% O2) oxygen tension. We found that 3 h of exposure to the low O2 tension increased EPO mRNA levels about 20-fold and the three VEGF (-180, -164, -120) mRNA levels, on average, about fourfold. Staurosporine did not change EPO and VEGF mRNA levels at 20% O2, but in a concentration-dependent manner, decreased EPO and VEGF mRNA at 1% O2 with IC50 values of 30 nM and 1000 nM, respectively. In the presence of 1% O2, genistein decreased EPO mRNA and VEGF mRNA levels with IC50 values of about 36 and 360 microM, respectively. Although mRNA levels for glycerine aldehyde phosphatehydrogenase (GAPDH) were not changed, staurosporine and genistein inhibited uridine incorporation into total RNA with IC50 values of about 1 microM and 100 microM, respectively. Comparison with the transcription inhibitor actinomycin D suggested that the effects of both kinase inhibitors on VEGF mRNA but not on EPO mRNA levels could be attributed to the non-specific inhibition of transcription in hepatocytes. These findings suggest that a kinase activity is specifically involved in the O2-dependent control of EPO gene expression but not of VEGF gene expression in hepatocytes.

Alkaloids↗
PubMed1996

Endothelins inhibit cyclic-AMP induced renin gene expression in cultured mouse juxtaglomerular cells.

We have recently described that endothelins-1 to -3 equipotently inhibit cAMP stimulated renin secretion from cultured mouse juxtaglomerular cells by a process involving phospholipase C activation. This study examined the influence of endothelin-2 on renin gene expression in renal juxtaglomerular cells. To this end we semiquantitated renin mRNA levels by competitive RT-PCR in primary cultures of mouse renal juxtaglomerular cells after 20 hours of incubation. We found that endothelin-2 (0.1 to 100 nmol/liter) did not change basal renin gene expression. The adenylate cyclase activator forskolin (3 mumol/ liter) increased renin mRNA levels to 400% of the controls and this stimulation was dose-dependently attenuated by ET-2 to 250% of the control value. The effect of ET-2 was mimicked by the ETB-receptor agonist sarafotoxin S6c. The kinase inhibitor staurosporine (100 nmol/ liter) increased renin secretion and renin mRNA levels. Combination of staurosporine with forskolin produced the same effects on renin secretion and renin mRNA levels as did staurosporine alone. In the presence of both forskolin and staurosporine ET-2 had no significant effect on renin secretion and renin gene expression. The phorbol ester PMA (30 nmol/ liter), which was used to stimulate protein kinase C activity, attenuated cAMP stimulated renin secretion and renin mRNA levels. Lowering the extracellular concentration of calcium by the addition of 1 mmol/liter EGTA did not inhibit the effect of ET-2 on cAMP induced renin secretion and renin gene expression. These findings suggest that endothelins inhibit cAMP stimulated renin gene expression by an event that is mediated via ETB receptors. This inhibitory effect may in part involve protein kinase C activation.

Animals↗
PubMed1996

Hypotonic swelling or stretch does not change cytosolic calcium in mouse renal juxtaglomerular cells.

This study aimed to examine the influence of cell swelling and of direct mechanical stretch on the cytosolic calcium concentration in mouse renal juxtaglomerular cells. To this end JG cells located in isolated mouse renal afferent arterioles were exposed to hypotonic extracellular fluid to cause cell swelling or were mechanically stretched and cytosolic calcium was monitored with fura-2 calcium microspectrofluorimetry. None of the above mentioned manoeuvres caused an increase of cytosolic calcium in the juxtaglomerular cells, which all responded to ionomycin (5 micrograms mL-1) with a marked calcium mobilization. Exposure of cultured rat renal mesangial cells to hypotonic buffer or direct mechanical stress increased cytosolic calcium in 90% of the cells under investigation. These findings suggest that cell swelling or an increased stretch of the plasma membrane of juxtaglomerular cells located in renal afferent arterioles does not lead to measurable increases of the cytosolic calcium concentration. It appears less likely therefore that a membrane-stretch regulated calcium influx has a major functional role in JG cells.

Animals↗
PubMed1996

Angiotensin II receptor gene expression in hypertrophied left ventricles of rat hearts.

OBJECTIVE: To examine the expression of angiotensin II AT1a, AT1b and AT2 receptor genes in the left ventricles of rats subjected to ventricular pressure overloading induced by aortic banding for 6 weeks and then 6 weeks medical treatment. RESULTS: Aortic banding was related to an increase in relative weight of the left ventricle from 1.73 +/- 0.06 (sham-operated) to 2.81 +/- 0.25 g/kg, an increase in beta-myosin: alpha-myosin messenger RNA (mRNA) ratio from 0.30 +/- 0.02 to 1.94 +/- 0.55 and an 18-fold increase in left ventricular atrial natriuretic peptide mRNA levels. In contrast, left ventricular pressure overload hypertrophy was not related to a significant change in the abundance of AT1a and AT1b mRNA, which were expressed in a relative ratio of 5:1. Similarly, the abundance of AT2 mRNA was not significantly changed in hypertrophied ventricles. In rats receiving the angiotensin II AT, receptor antagonist losartan (40 mg/kg) for 6 weeks after banding, relative heart weights were 2.39 +/- 0.14 g/kg, the beta-myosin: alpha-myosin ratio was 1.04 +/- 0.20 and atrial natriuretic peptide mRNA levels displayed a blunted increase (11-fold over sham-treated controls), documenting a significant amelioration of left ventricular hypertrophy by blockade of the AT1 receptor. CONCLUSION: Losartan treatment in parallel did not affect AT1a, AT1b and AT2 receptor mRNA levels, which were not different from those in vehicle-treated or sham-treated controls. These findings confirm that left ventricular hypertrophy in the rat is associated with increased ventricular expression of beta-myosin and of atrial natriuretic peptide and with reduced expression of alpha-myosin. Despite these significant changes in cardiac gene expression no alteration was observed in AT1a, AT1b and AT2 receptor mRNA levels.

Angiotensin II↗
PubMed1996

Regulation of renin synthesis in the juxtaglomerular cells.

Renin synthesis in vivo is feedback regulated by the plasma angiotensin II concentration, the intrarenal pressure, the salt loading of the organism and the macula densa mechanism. At the level of renal juxtaglomerular cells renin synthesis is regulated by cyclic AMP, by nitric oxide and by the cytosolic calcium concentration. Cyclic AMP and nitric oxide are stimulators, whereas calcium is an inhibitor of renin synthesis.

Animals↗
PubMed1996

Effect of amlodipine on renin secretion and renin gene expression in rats.

1. This study was done to characterize the influence of calcium channel blockade on renin secretion and renin gene expression in normal rats and rats with renovascular hypertension. To this end we studied the effects of the 1,4-dihydropyridine derivative, amlodipine, on plasma renin activity and renal renin m-RNA levels in normal rats and rats with unilateral renal hypoperfusion induced by applying 0.2 mm left renal artery clips over four days. 2. In normotensive rats, amlodipine significantly decreased basal blood pressure by about 20 mmHg when applied in a concentration of 5, 15 and 45 mg kg-1. Plasma renin activity and also renin mRNA levels were not changed after application of 5 mg kg-1 of amlodipine. However, at a concentration of 15 or 45 mg kg-1, amlodipine, significantly increased not only plasma renin activity by about 250% and 300%, but also renin mRNA levels by about 100% and 500%. The action of amlodipine on all these parameters was maximal after 24 h. Treatment with amlodipine in a concentration of 15 mg kg-1 also increased renin immunoreactive areas in the kidney cortex by retrograde recruitment of renin expressing cells in the afferent arterioles. 3. In 2kidney-1 clip rats, systolic blood pressure rose continuously whilst plasma renin activity and renin m-RNA in the clipped kidney increased transiently and renin m-RNA in the contralateral kidney was constantly suppressed. Amlodipine at a concentration of 15 mg kg-1 markedly attenuated the increase of blood pressure in 2kidney-1 clip rats, produced an almost additive effect on plasma renin activity and showed a tendency to increase renin m-RNA levels in the clipped kidneys. Renin m-RNA levels in the contralateral kidney were also significantly suppressed in the animals receiving additional treatment with amlodipine. 4. These findings suggest that inhibition of calcium channels by amlodipine stimulates renin secretion and renin gene expression in vivo. These stimulatory effects are almost additive to the changes of renin secretion occurring after an unilateral fall of renal perfusion pressure.

Amlodipine↗
PubMed1996

Cobalt but not hypoxia stimulates PDGF gene expression in rats.

This study was done to investigate the influence of different forms of acute tissue hypoxia on the expression of platelet-derived growth factor (PDGF) A chain (PDGF-A) and PDGF B chain (PDGF-B) genes in different rat organs. We found that acute normobaric hypoxia (8% O2), carbon monoxide inhalation (0.1% CO), or lowering the hematocrit to 12% for 6 h had no effect on PDGF-A or PDGF-B gene expression in lung, heart, kidney, and liver of Sprague-Dawley rats. Subcutaneous administration of cobaltous chloride dose dependently increased PDGF-B mRNA by 125% in lungs, by 60% in kidneys, but not in heart and liver. These findings suggest that acute tissue hypoxygenation is not a significant stimulus for PDGF-A and PDGF-B gene expression in these major rat organs. Cobalt appears to cause a tissue-specific increase of PDGF-B gene expression.

Administration, Cutaneous↗
PubMed1996

Prostaglandins stimulate renin secretion and renin mRNA in mouse renal juxtaglomerular cells.

This study examined 1) effects of prostaglandins (PG) on renin secretion and renin gene expression from isolated juxtaglomerular granular cells and 2) expression of cyclooxygenases in juxtaglomerular structures. Incubation of granular cell cultures with PGE2, -I2, -F2 alpha, and thromboxane B2 identified PGI2 and PGE2 as stimulators of renin secretion; the effects were dose and time dependent. PGE2 also increased renin mRNA accumulation time and dose dependent. PGE2 and PGI2 activated adenylate cyclase concentration dependent in granular cells. PGE2 stimulations of renin secretion and renin mRNA were nonadditive to those of forskolin and were inhibited by endothelin. The findings are compatible with cellular actions through adenosine 3',5'-cyclic monophosphate (cAMP). On total RNA harvested from whole kidneys, from microdisected glomeruli with attached afferent arterioles and from mesangial cells in primary culture, reverse transcription-polymerase chain reaction revealed significant expression of cyclooxygenase I and II. By direct interaction with PG receptors on renal juxtaglomerular cells, PGE2 and PGI2 can act as potent and rapid stimulators of renin secretion and renin mRNA probably through cAMP-dependent pathways.

Adenylyl Cyclases↗
PubMed1996

Messenger ribonucleic acid levels of collagenase (MMP-13) and matrilysin (MMP-7) in virgin, pregnant, and postpartum uterus and cervix of rat.

Evidence indicates that matrix metalloproteinases (MMPs) are essentially involved in the postpartum involution of the uterus. As little information exists about the gene regulation of those MMPs in the uterus, this study aimed to characterize the time course of messenger RNA (mRNA) levels of rat collagenase (MMP-13) and matrilysin (MMP-7) in virgin, late pregnant (18th and 21st day), and postpartum rats (1, 2, 3, and 4 days postpartum). Rat collagenase (MMP-13) mRNA levels were very low in virgin and pregnant animals, but increased transiently 30-fold postpartum, reaching a maximum on the second day postpartum. The temporal course of mRNA levels of matrilysin (MMP-7) shows similarity with that of collagenase mRNA levels, but at any stage the abundance of matrilysin mRNA was at least 100-fold higher than that of collagenase. In virgin animals, matrilysin mRNA levels were dependent on the estrous cycle, being 3- to 4-fold higher in the estrous and diestrous stages than during metestrus. MMP-7 shows an approximately 25-fold induction when comparing the mRNA levels in late pregnancy and 2 days postpartum. In cervexes of virgin, pregnant, and postpartum groups, collagenase mRNA was not detectable. Matrilysin in cervix shows temporal mRNA expression similar to that in uterus, with a maximum on day 1 postpartum. In cervix, we found a 14-fold induction when comparing levels in late pregnancy and those 1 day postpartum. Taken together, our findings suggest that the increased activity of MMPs in the postpartum uterus is due to a strong increase in the mRNA levels of MMP-13 and MMP-7.

Animals↗
PubMed1996

Role of endothelins for renin regulation.

Endothelins 1, 2, and 3 did not affect basal renin secretion, but selectively inhibited to a similar extent both cAMP-stimulated renin secretion and renin gene expression in isolated renal juxtaglomerular cells. In isolated perfused rat kidneys and after cAMP-stimulated renin secretion using isoproterenol, endothelins inhibited basal renin secretion at a perfusion pressure of 80 mm Hg. Endothelin's main action is mediated via the endothelin ETB receptor. It involves activation of phospholipase C, intracellular calcium mobilization in juxtaglomerular cells that is dependent on extracellular calcium and associated with prominent calcium-activated chloride currents, and subsequent processes. In normal rats and in rats with unilateral renal artery clips, a nonselective inhibitor of endothelin receptors, Ro 47-0203, did not significantly change renin secretion and renal renin gene expression, despite complete abolition of the vasoconstrictive and renin inhibitory action of exogenous endothelins by this drug in isolated perfused rat kidneys. In spite of a marked renin inhibitory efficacy of exogenous endothelins in vitro (isolated renal juxtaglomerular cells, isolated perfused rat kidney), endogenous endothelins play no relevant regulatory role in renin secretion and renin gene expression in normal and hypoperfused rat kidneys in vivo. However, endothelins may be of physiological relevance for the development of hypertension upon renal artery stenosis.

Animals↗
PubMed1995

Rat renin gene transcription is initiated at a single start site.

The promoter region of the renin gene in man, mouse and rat contains several putative transcription start sites, which in mouse have been shown to be tissue specific and differently regulated. To investigate which of these start sites are used during stimulation of renin gene transcription by the major physiological control factors, we determined the transcription start sites of rat renin in the kidney and adrenal glands by RNase protection using a cRNA probe spanning 387 bases upstream and 121 bases downstream from the canonical transcription initiation site. To stimulate renin gene expression, we used renal artery stenosis, angiotensin II antagonists, furosemide and isoprenaline infusions and low sodium diet. Our results suggest that only one TATA box is functional in rat kidney and adrenal.

Adrenal Glands↗
PubMed1995

Tonic stimulation of renin gene expression by nitric oxide is counteracted by tonic inhibition through angiotensin II.

This study was designed to examine the possible involvement of prostaglandins and nitric oxide (NO) in the renin stimulatory effect of angiotensin II (AngII) antagonists. To this end, plasma renin activities (PRAs) and renal renin mRNA levels were assayed in rats that were treated with the Ang-converting enzyme inhibitor ramipril or with the AngII AT1-receptor antagonist losartan. Ramipril and losartan increased PRA values from 7.5 +/- 1.6 to 86 +/- 6 and 78 +/- 22 ng of AngI per h per ml and renin mRNA levels from 112 +/- 9% to 391 +/- 20% and 317 +/- 10%, respectively. Inhibition of prostaglandin formation with indomethacin did not influence basal or ramipril-affected PRA. Basal renin mRNA levels also were unchanged by indomethacin, while increases in renin mRNA levels after ramipril treatment were slightly reduced by indomethacin. Inhibition of NO synthase by nitro-L-arginine methyl ester (L-NAME) reduced PRA values to 3.2 +/- 0.9, 34 +/- 13, and 12.1 +/- 2.7 ng of AngI per h per ml in control, ramipril-treated, and losartan-treated animals, respectively. Renin mRNA levels were reduced to 77 +/- 14% under basal conditions and ramipril- and losartan-induced increases in renin mRNA levels were completely blunted after addition of L-NAME. The AngII antagonists, furthermore, induced an upstream recruitment of renin-expressing cells in the renal afferent arterioles, which was also blunted by L-NAME. These findings suggest that renin mRNA levels are tonically increased by NO and that the action of NO is counteracted by AngII.

Analysis of Variance↗
PubMed1995

Differential regulation of cytosolic calcium between afferent arteriol ar smooth muscle cells from mouse kidney.

Using a combination of whole-cell patch-clamping and calcium microspectrofluorimetry we have examined the calcium regulation and calcium-activated electrical currents in smooth muscle cells along mouse renal afferent arterioles. In cells located at a distance up to 50microm from the glomerular vascular pole, guanosine 5'-[gamma-thio]triphosphate, (GTP[tau -S], 100micromol/l) and angiotensin II (1micromol/l) evoked internal calcium mobilization and oscillations of intracellular calcium concentration. Membrane depolarization up to +30mV did not increase cytosolic free calcium in these cells, which displayed calcium-activated chloride currents. In cells located more distant than 100microm from the glomerular vascular pole, GTP[tau -S] did not increase cytosolic calcium at negative membrane potentials. Depolarization of these cells to 0mV or positive membrane potentials increased intracellular calcium in a dihydropyridine-sensitive manner. These cells responded to angiotensin II with single calcium transients and also displayed calcium-activated chloride currents. These findings suggest that intracellular calcium is differentially regulated between afferent arteriolar smooth muscle cells from mouse kidney: in smooth muscle cells which are distant from the glomerular vascular pole, cytosolic calcium is increased primarily via calcium influx through potential-operated calcium channels, whilst in cells which are close to the vascular pole intracellular calcium is elevated predominantly via mobilization from internal stores. Both cell types are equipped with receptors for angiotensin II and possess calcium-activated chloride channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Prostaglandins are involved in the stimulation of renin gene expression in 2 kidney-1 clip rats.

This study was done to obtain information about a possible involvement of prostaglandins in the renal baroreceptor mechanism regulating renin secretion and renin gene expression. To this end the effect of the cyclooxygenase inhibition was examined on renin secretion and on renal renin gene expression in 2 kidney-1 clip rats. The influences of the cyclooxygenase inhibitors indomethacin (2mg/kg twice a day) and meclofenamate (8 mg/kg twice a day) on renal renin m-RNA levels, on plasma renin activity (PRA) and on blood pressure were measured 2 days after clipping the left renal arteries of male Sprague-Dawley rats with 0.2 mm clips. In sham-clipped animals, indomethacin and meclofenamate had no significant effect on basal PRA and renin m-RNA levels. In vehicle-treated animals unilateral renal artery clipping increased blood pressure from 120 +/- 4.1 to 150 +/- 6.1 mmHg, increased PR6A from 7.4 +/- 1.6 to 27.6 +/- 3.8 as expressed in nanograms of angiotensin I per hour per millilitre, increased renin m-RNA levels of clipped kidneys from 105 +/- 5.9% of standard to 482.6 +/- 56% of standard and decreased renin m-RNA levels of contralateral kidneys from 116 +/- 9.7% of standard to 34 +/- 9.0% of standard. While blood pressure, PRA and renin m-RNA levels of the contralateral kidneys were virtually unchanged by the cyclooxygenase inhibitors indomethacin and meclofenamate, renin gene expression in the clipped kidney was markedly influenced by inhibition of prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗