Biomedical subjects

B Kaissling

Publications and source records attributed to B Kaissling.

At least 55 records · Page 3Linked to original sources

PubMed1996

Chronic metabolic acidosis increases NHE3 protein abundance in rat kidney.

Chronic metabolic acidosis increases the activity of the proximal tubule apical membrane Na/H antiporter, which is encoded predominantly by the NHE3 isoform. The present studies examined the effect of chronic metabolic acidosis on apical membrane NHE3 protein abundance in rats. Rats subjected to NH4Cl in their drinking water developed a metabolic acidosis, which decreased in magnitude over 14 days. During this time, renal cortical brush-border membrane NHE3 protein abundance, assessed by Western blot, increased progressively (28% at 3 days, 59% at 7 days, and 90% at 14 days). Immunohistochemistry revealed that the acidosis-induced increase in NHE3 abundance occurred in the apical membranes of the S1 and S2 segments of the proximal tubule and the thick ascending limb. NHE3 mRNA abundance was not significantly increased in these animals, whereas phosphoenolpyruvate carboxykinase and glyceraldehyde-3-phosphate dehydrogenase mRNA abundances were significantly increased. These studies demonstrate that the increase in Na/H antiporter activity seen in metabolic acidosis involves an increase in NHE3 protein abundance, which is distributed along the proximal tubule and the thick ascending limb. In addition, these studies suggest that a component of this adaptation is unrelated to changes in NHE3 mRNA abundance.

Acidosis↗

PubMed1996

Molecular mechanisms in the regulation of renal proximal tubular Na/phosphate cotransport.

Renal proximal tubular Na/phosphate cotransport is the key target in the control of renal phosphate handling. Using molecular tools for the type II Na/phosphate cotransporter, it could be documented that altered brush border membrane phosphate transport reflects a state of altered brush border expression of the specific transporter molecule. This alteration is either the consequence of specific membrane insertion/retrieval processes and/or reflects states of altered synthesisdegradation of the transporter.

Absorption↗

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

Ecto-5'-nucleotidase is expressed by pericytes and fibroblasts in the rat heart.

Ecto-5'-nucleotidase is anchored at the outer surface of cell membranes and thus its reaction product adenosine is released into the extracellular space. Extracellular adenosine displays via specific receptors a wide range of physiological effects in heart. There are discrepancies in the literature concerning the distribution of ecto-5'-nucleotidase in heart. Since we suspected that these may be due to technical problems, in the present study on ecto-5'-nucleotidase in rat heart we attempted to circumvent some technical pitfalls. Good preservation of the tissue with open capillary lumina, providing a clear identification of endothelium, was obtained by perfusion fixation. At the light microscopic level, the distribution of ecto-5'-nucleotidase studied by enzyme histochemistry and immunohistochemistry using a monoclonal and a polyclonal antibody yielded congruent results. The enzyme was rather homogeneously distributed throughout the myocardium, with a slightly higher incidence of stained cells in the outer thirds than in the inner third of the wall. Consistently high levels of ecto-5'-nucleotidase were seen only in interstitial cells. The walls of large vessels and heart muscle cells were constantly negative for ecto-5'-nucleotidase. The endothelia of capillaries were mostly negative but a few profiles occasionally displayed a weak immunoreaction. The interstitial cells staining positive for ecto-5'-nucleotidase could be identified as pericytes and as fibroblasts according to their shapes and localizations. The immunoreactivity of fibroblasts was confirmed by electron microscopy. These data indicate that adenosine may be formed extracellularly in the interstitium of the myocardium, where it would have direct access to important targets such as myocytes, arterioles and nerve endings.

5'-Nucleotidase↗

PubMed1995

Modulation of salt transport rate affects DNA synthesis in vivo in rat renal tubules.

In adult male Wistar rats we investigated whether cell proliferation contributes to salt load-induced hypertrophy of distal tubules. In one treatment group salt transport in the thick ascending limb (TAL) was inhibited by furosemide (7.5 mg/100 g body wt/24 hr, via osmotic minipump) and stimulated in the successive distal segments by simultaneous high salt intake (F + Salt). Controls without furosemide treatment had a standard salt intake. All animals received the thymidine analog bromodeoxyuridine (BrdU) during 24 and 72 hours, respectively. In cryostat sections of the perfusion-fixed kidneys DNA synthesis was assessed by immunohistochemistry for BrdU, and for endogenous proliferating cellular nuclear antigen (PCNA). Incidence of BrdU- and PCNA-labeled nuclei were quantified in proximal tubules, medullary TAL, and cortical distal segments downstream the TAL. In control animals low labeling indices were found in all investigated segments. After 24 and 72 hours of F + Salt, indices of labeled nuclei were markedly increased in distal segments downstream the TAL, whereas they were significantly reduced in TAL. In proximal tubules increased DNA synthesis rate was apparent only after 72 hours. The data demonstrate that (1.) DNA synthesis rate in nephron segments in vivo varies in parallel with changes of their salt transport activity; (2.) increased DNA synthesis, thus probably cellular proliferation, is a component of the structural response of nephron segments following increased salt transport activity.

Animals↗

PubMed1995

Expression of NHE-3 in the apical membrane of rat renal proximal tubule and thick ascending limb.

Apical membrane Na/H exchange is a principal mechanism of renal proximal tubule Na absorption and H secretion, and thick ascending limb H secretion. Based on current data on Na/H exchanger isoforms (NHE-1 to 5), NHE-3 is the likeliest candidate for the apical membrane isoform. The present study localizes NHE-3 in rat kidney using polyclonal antisera against cytoplasmic epitopes of rat NHE-3. These antisera recognized an approximately 87 kD protein in Na/H exchanger-deficient cells transfected with the rat NHE-3 gene but not in mock-transfected cells. All antisera labeled an approximately 87 kD protein in plasma membranes from cortex and outer medulla. Fractionation of cortical membranes showed labeling in apical but not basolateral membranes. Cross linking studies suggested existence of oligomeric forms of the transporter. Immunohistochemistry showed strong staining of the apical membrane of S1 convoluted, and S2 convoluted tubule with lesser staining of the S2 straight tubule and absent staining of S3. Weak staining was observed in thin descending limbs in the inner stripe and intense staining was seen in the apical membrane of medullary and cortical thick ascending limbs. NHE-3 staining was absent in the remainder of the nephron. In summary, NHE-3 is the isoform responsible for NaCl and NaHCO3 absorption in the proximal convoluted tubule, and NaHCO absorption in the thick ascending limb. In the S3 proximal tubule and the distal convoluted tubule, apical membrane Na/H exchange activity is likely mediated by other isoform(s) of the NHE family.

Amino Acid Sequence↗

PubMed1995

Parathyroid hormone action on phosphate transporter mRNA and protein in rat renal proximal tubules.

The inhibitory action of parathyroid hormone (PTH) on Pi reabsorption in the renal proximal tubule is accompanied by a specific decrease in Na-Pi cotransport at the apical brush-border membrane (BBM). It is not known whether this decrease represents decreased activity of Na-Pi cotransporters already present in the BBM or whether the number of cotransporters is decreased. The present study of the molecular mechanism of PTH action made use of a specific cDNA probe and antiserum to a rat renal Na-Pi cotransporter (NaPi-2). Three groups of rats were used: intact controls, chronically parathyroidectomized (PTX), and PTX rats treated acutely (2 h) with bovine PTH-(1--34). Na-Pi cotransport by isolated renal BBM vesicles was increased to 1,315 +/- 44 in PTX rats, compared with 721 +/- 94 pmol.mg-1.10 s-1 in controls (P < 0.002), and was returned to control levels by PTH. Western blots of these BBM showed that PTX caused a 2.8-fold increase in NaPi-2 protein content, which was reduced to control levels by PTH. Immunohistochemistry of perfusion-fixed kidneys showed NaPi-2-specific immunofluorescence exclusively in apical BBM of proximal tubules. Expression of NaPi-2 protein at these sites was increased in PTX rats and decreased after PTH treatment. Northern analysis of total RNA showed that the abundance of NaPi-2-specific mRNA was not changed by PTX but there was a small decrease in response to PTH. The data indicate that PTH regulation of renal Na-Pi cotransport is determined by changes in expression of NaPi-2 protein in the renal BBM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Distribution of ecto-5'-nucleotidase in the rat liver: effect of anaemia.

In the kidney a striking parallel exists between the expression of ecto-5'-nucleotidase and of erythropoietin by renal fibroblasts. It was therefore hypothesized that the expression of ecto-5'-nucleotidase in fibroblasts might be controlled by oxygen tension. In order to test this hypothesis, we examined the distribution of the enzyme in a tissue which displays a defined zonation in respect to oxygen tension, namely in the liver; anaemia was used in order to exaggerate this zonation. The distribution of ecto-5'-nucleotidase was investigated by light and electron microscopy using enzyme and immunohistochemical methods in the livers of healthy and of anaemic rats. Anaemia was produced by haemolysis combined with X-ray irradiation. The enzyme was detected in the bile canaliculi, in the connective tissue of the portal triads and of the central veins, and in fat-storing cells probably corresponding to a special form of fibroblasts. In healthy animals the perisinusoidal ecto-5'-nucleotidase activity was slightly higher in the pericentral than in the periportal area of the acinus whereas the inverse was observed for the staining of bile canaliculi. Anaemia provoked an increase of ecto-5'-nucleotidase in fat-storing cells in the pericentral zone of the acinus and in fibroblasts around the central veins, resulting in steepended gradients along the sinusoids. The intralobular gradient of ecto-5'-nucleotidase in perisinusoidal cells and the effect thereon of anaemia suggest that the expression of the ecto-5'-nucleotidase might be directly or indirectly controlled by local oxygen tension.

5'-Nucleotidase↗

PubMed1994

Low-Pi diet increases the abundance of an apical protein in rat proximal-tubular S3 segments.

Dietary phosphate (Pi) restriction is associated with an adaptive increase in proximal-tubular apical brush-border membrane (BBM) sodium-dependent Pi transport (Na-Pi cotransport). Adaptation to Pi restriction is dependent on de novo protein synthesis; however, it is not known whether the proteins involved represent newly synthesized Na-Pi cotransporters or some other (regulatory) proteins. Recently the cDNA for a Na-Pi cotransport system of rabbit kidney cortex (system NaPi-1) has been identified by expression cloning. The purpose of this study was to determine if the adaptive increase in Na-Pi cotransport in response to dietary Pi restriction in the rat is associated with an increase in the abundance of a NaPi-1-related protein. To answer this question we took advantage of the cross-reactivity of polyclonal antibodies raised against a C-terminal peptide of the NaPi-1 protein with a protein of BBM isolated from rat kidney cortex. On Western blots, a positive reaction with a protein with an apparent molecular mass of 100 kDa was observed in BBM isolated from juxtamedullary cortex and, to a lesser extent, in BBM isolated from superficial cortex. In immunohistochemical studies anti-(NaPi-1)-antiserum-mediated immunofluorescence was observed predominantly in S3 segments where the immunoreaction was restricted to the brush borders. Compared to control BBM, in BBM isolated from the juxtamedullary cortex of rats fed a low-Pi diet, there was a twofold increase in the abundance of the 100-kDa protein. In the same membrane vesicles Na-Pi cotransport was increased threefold. The results of this study demonstrate specific expression of a 100-kDa apical protein in S3 cells of rat proximal tubules. Increased abundance of the 100-kDa protein due to chronic Pi restriction suggests an involvement of this protein in the (chronic) adaptive response of S3 cells to a low-Pi diet.

Adaptation, Physiological↗

PubMed1994

Role of the macula densa in the control of renal renin gene expression in two-kidney/one-clip rats.

This study was designed to examine whether macula densa function is involved in the changes of renal renin gene expression upon acute hypoperfusion of one kidney. To block macula densa function, rats with free access to salt and water were subcutaneously infused with furosemide (12 mg/day) for 6 days. Then, 4 days after the start of the infusion, the left renal arteries were clipped with 0.2-mm silver clips and renin mRNA levels in ipsilateral and contralateral kidneys, as well as plasma renin activities (PRA), were determined 48 h after clipping. In non-clipped animals furosemide increased PRA from 10 to 47 ng angiotensin I.h-1.ml-1 and raised renin mRNA levels in both kidneys 2.5-fold. In vehicle-infused animals, clipping of the left renal artery increased PRA to 37 ng angiotensin I.h-1.ml-1 and led to a 5-fold rise of renin mRNA levels in the ipsilateral kidneys and to a suppression to 20% of the control values in the contralateral kidneys. PRA values in clipped and furosemide-infused animals were 45 ng angiotensin I.h-1.ml-1. In these animals renin mRNA levels increased in the ipsilateral kidneys to similar absolute values as in vehicle-infused rats, whilst contralateral renin mRNA levels fell to about 25% of the respective controls. These findings indicate that the stimulations of renin gene expression by inhibition of macula densa salt transport and by renal artery clipping are not additive, suggesting that the macula densa mechanism may participate in the stimulation of renin gene expression upon hypoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

PubMed1994

Morphology and distribution of ecto-5'-nucleotidase-positive cells in the rat choroid plexus.

The aim of this report was to find out whether adenosine can be produced locally in the choroid plexus of rats. Therefore we investigated the distribution of the enzyme ecto-5'-nucleotidase which hydrolyzes extracellular adenosine monophosphate to adenosine and phosphate. Enzyme activity histochemistry and immunohistochemistry demonstrated that ecto-5'-nucleotidase is present in the stroma but not in the epithelium. The positive cells in the stroma were identified as fibroblasts by their localization and by their shape. Double-labelling immunohistochemistry actually showed that ecto-5'-nucleotidase was absent from MHC class II-positive cells and from vessel walls. These data indicate that adenosine may be produced in the choroid plexus, and specifically in the interstitium. From there, adenosine would have direct access to nerves, immune cells, the epithelium and microvessels. Because adenosine has been reported to modulate blood supply and the rate of production of cerebrospinal fluid, a local control mechanism involving adenosine might operate in the choroid plexus in a similar way to that described in other tissues. Effects of adenosine on nerves and immune cells are discussed. The exclusive presence of ecto-5'-nucleotidase in the fibroblasts that are in contact with choroid plexus epithelium suggests that the expression of the enzyme is controlled by factors produced by epithelial cells, for instance by extracellular nucleotides.

5'-Nucleotidase↗

PubMed1994

Renal autacoids are involved in the stimulation of renin gene expression by low perfusion pressure.

This study aimed to examine the role of local autacoids for the regulation of renin secretion and renin gene expression by the renal perfusion pressure. To this end the effects of unilateral reduction of renal perfusion by 0.2 mm clips on plasma renin activity and on renal renin mRNA levels were examined in rats treated with the cyclooxygenase inhibitor meclofenamate (8 mg/kg body wt, twice a day), with the NO-synthase inhibitor nitro-L-arginine-methylester (L-NAME, 40 mg/kg body wt, twice a day) or with a combination of both. L-NAME alone decreased basal PRA values from 9.9 to 5.4 ng Ang I/hr x ml, while meclofenamate alone and the combination meclofenamate/L-NAME had no consistent effect on basal PRA. Unilateral renal artery clipping increased PRA values from 9.9 ng Ang I/hr x ml to 34, 27, and 16 ng Ang I/hr x ml in vehicle, meclofenamate, and L-NAME treated animals, respectively, but did not increase PRA in meclofenamate/L-NAME treated rats (9.5 ng Ang I/hr x ml). Renal renin mRNA levels in the clipped kidneys increased 4.8-, 2.6-, 2.5- and 1.8-fold in the clipped kidneys in vehicle, meclofenamate, L-NAME and meclofenamate/L-NAME injected animals, respectively. These findings indicate that both the inhibition of prostaglandin synthesis and of the formation of endothelium-derived relaxing factor (EDRF) attenuate the increase of renin gene expression and of renin secretion in response to acute unilateral renal hypoperfusion and that the effects of both maneuvers are additive.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Characterization and distribution of interstitial cell types in the renal cortex of rats.

A precise classification of the cellular components of the cortical peritubular interstitium is missing in spite of its physiological and pathophysiological importance. By combining electronmicroscopy and immunohistochemistry we attempted to better identify and localize the different interstitial cell types in rat kidney, with special attention to the cortex. Antibodies against common leukocyte antigen (OX1), a macrophage antigen (ED 2), MHC class II antigen (OX6) and ecto-5'-nucleotidase were applied to cryostat sections. The two latter antibodies were used additionally in electron microscopy. Four groups of cell types were identified that displayed distinct antigenic patterns, distributions and morphological features. They were identified as fibroblasts, dendritic cells, macrophages and lymphocytes. Fibroblasts and dendritic cells constituted the most abundant cell types in the cortex and outer medulla, and they were rather uniformly distributed in these zones throughout the peritubular interstitium, where macrophages were very scarce. The latter were abundant in the connective tissue of large vessels and of the pelvic wall. The incidence of lymphocytes was generally low. These data may be helpful on the one hand for the further phenotypic characterization of renal interstitial cells and on the other hand for the evaluation of the roles of those cells in pathological processes.

Animals↗

PubMed1994

Role of renal nerves for the expression of renin in adult rat kidney.

Utilizing a combination of mechanical and chemical unilateral denervation, we have examined the relevance of renal innervation for the expression of renin in kidneys of adult rats. Renal denervation led to a reduction by 57 +/- 4% of renin-containing areas in denervated kidneys as quantitated by morphometry of kidney sections immunoreactive against a polyclonal antirenin antibody. Preprorenin mRNA content in the denervated kidneys fell to 46 +/- 7% of the contralateral innervated kidneys. Treatment of rats with the beta 1-adrenoreceptor antagonist metoprolol (100 mg.kg-1.day-1) for 2 days decreased renal renin mRNA levels to 71% of control levels. Unilateral renal denervation led to a further decrease of renin mRNA levels also in metoprolol-treated animals to 60% of the values found in the contralateral kidneys. Hypotensive hemorrhage led to a 1.4-fold increase of renin mRNA in the kidneys of sham-treated animals. In unilaterally denervated rats renin mRNA increased to levels similar to those in sham-operated animals in both denervated and in contralateral innervated kidneys in response to bleeding. As a consequence, the ratio of abundance of renin mRNA in the denervated to the innervated kidneys rose to 86 +/- 7%. Pretreatment of the animals with metoprolol, on the other hand, prevented the rise of renin mRNA in response to hypotensive hemorrhage. Our findings suggest that in the adult organism renal neural input significantly contributes to the expression of renin under basal conditions, while it appears to be of less importance for stimulation of renin gene expression by severe blood loss.

Analysis of Variance↗

PubMed1994

Expression of Na-P(i) cotransport in rat kidney: localization by RT-PCR and immunohistochemistry.

We have recently identified a rat kidney cortex Na-dependent transport system for phosphate (P(i)) by expression cloning (NaP(i)-2) (S. Magagnin, A. Werner, D. Markovich, V. Sorribas, G. Stange, J. Biber, and H. Murer. Proc. Natl. Acad. Sci. USA 90: 5979, 1993). In this study we have used reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry to establish the sites of expression of the NaP(i)-2-related mRNA and protein. RT-PCR was performed with single microdissected nephron segments. From these experiments we conclude that NaP(i)-2 mRNA is predominantly expressed in the proximal tubules of superficial and deep nephrons. No NaP(i)-2 mRNA was detected in the thick ascending limb of Henle's loop; however, faint NaP(i)-2 related PCR products were also observed in collecting ducts. Expression of the NaP(i)-2 protein was examined with the use of polyclonal antibodies raised against synthetic NaP(i)-2-derived peptides. Strong specific anti-NaP(i)-2 antiserum-mediated immunofluorescence was found in the convoluted part of proximal tubules and gradually decreased along the straight part. Immunofluorescence indicated that the NaP(i)-2 protein is present in the brush border of proximal tubular cells. In addition, NaP(i)-2-specific immunofluorescence was also observed in subapical vesicles. The described distribution of the NaP(i)-2 protein is in agreement with previously described nephron sites of P(i) reabsorption in the rat kidney and therefore suggests that the NaP(i)-2 transport system represents an Na-P(i) cotransporter involved in proximal tubular apical transport of phosphate.

Animals↗

PubMed1994

Cellular mechanisms of acute and chronic adaptation of rat renal P(i) transporter to alterations in dietary P(i).

Recently, the cDNA for a Na-P(i) cotransport system of rat kidney cortex (NaPi-2) has been identified by expression cloning. Using polyclonal antibodies raised against this renal Na-P(i) cotransport system, and using the polymerase chain reaction after reverse transcription of mRNA in microdissected nephron segments, we recently demonstrated that NaPi-2-related mRNA and protein is expressed in the brush-border membranes (BBM) of the proximal tubules of rat kidney. The purpose of the present study was to study the cellular mechanisms involved in adaptation of rat renal Na-P(i) cotransporter to acute and chronic alterations in dietary P(i). Compared with rats fed chronically (7 days) a high-P(i) diet (1.2%), in rats fed chronically a low-P(i) (0.1%) diet the 3.4-fold increase in BBM Na-P(i) cotransport rate (chronic upregulation) was associated with a 2.2-fold increase in renal cortical NaPi-2 mRNA and a 4.9-fold increase in BBM NaPi-2 protein abundances. In contrast, compared with rats fed chronically (7 day) a high-P(i) diet, in rats fed acutely (2 h) a low-P(i) diet the 1.5-fold increase in Na-P(i) cotransport rate (acute upregulation) was associated with a 1.8-fold increase in NaPi-2 protein but no change in NaPi-2 mRNA abundance. Similarly, compared with rats fed chronically a low-P(i) diet, in rats fed acutely (2 h) a high-P(i) diet the 1.9-fold decrease in Na-P(i) cotransport rate (acute downregulation) was associated with a 3.8-fold decrease in NaPi-2 protein but no change in NaPi-2 mRNA abundance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

PubMed1993

Cellular components of the immune barrier in the spinal meninges and dorsal root ganglia of the normal rat: immunohistochemical (MHC class II) and electron-microscopic observations.

This report deals with the distribution, morphology and specific topical relationships of bone-marrow-derived cells (free cells) in the spinal meninges and dorsal root ganglia of the normal rat. The morphology of these cells has been studied by transmission and scanning electron microscopy. Cells expressing the major histocompatibility complex (MHC) class II gene product have been recognized by immunofluorescence. At the level of the transmission electron microscope, free cells are found in all layers of the meninges. Many of them display characteristic ultrastructural features of macrophages, whereas others show a highly vacuolated cytoplasm and are endowed with many processes. These elements lack a conspicuous lysosomal system and might represent dendritic cells. Scanning electron microscopy has revealed that free cells contact the cerebrospinal fluid via abundant cytoplasmic processes that cross the cell layers of the pia mater and of the arachnoid. Cells expressing the MHC class II antigen are also found in all layers of the meninges. They are particularly abundant in the layers immediately adjacent to the subarachnoid space, in the neighbourhood of dural vessels, along the spinal roots and in the dural funnels. In addition to the meninges, strong immunoreactivity for MHC class II antigen is observed in the dorsal root ganglia. The ultrastructural and immunohistochemical findings of this study suggest the existence of a well-developed system of immunological surveillance of the subarachnoid space and of the dorsal root ganglia.

Animals↗

PubMed1993

Furosemide stimulates renin expression in the kidneys of salt-supplemented rats.

This study was conducted to obtain information about a possible influence of salt transport by the thick ascending limb of Henle (TALH) and the macula densa on the expression of renin in the kidney. To this end, adult male rats were subcutaneously infused with furosemide (12 mg/24 h), an established inhibitor of TALH and macula densa salt transport, or with vehicle for 6 days. The animals had free access to chow, water and salt water (0.8% NaCl, 0.1% KCl) to maintain salt and water balance. Chronic furosemide treatment led to a 20-fold increase in urine flow rates and 50% increase in kidney weights, while urine osmolality decreased by 60% and body weight gain decreased by 40% in the furosemide-treated animals. Plasma renin activities increased from 2.9 +/- 0.5 ng angiotensin I h-1 ml-1 in controls to 10.6 +/- 2.2 ng angiotensin I h-1 ml-1 in furosemide-treated rats. In parallel, kidney areas immunoreactive for renin increased by 80% and the renal content of renin mRNA increased by 120% in the animals receiving furosemide. Under the assumption that the effects seen on renal renin expression were primarily due to the inhibition of TALH and macula densa function by furosemide, our findings suggest that salt transport across the TALH and macula densa exerts a negative control function not only on the secretion but also on the expression of renin in the kidney.

Animals↗