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K M Madsen

Publications and source records attributed to K M Madsen.

69 records · Page 4Linked to original sources
PubMed1985

Response of the medullary thick ascending limb to hypothyroidism in the rat.

Hypothyroidism in the rat is associated with a decrease in kidney size and weight. We have shown previously that this decrease involves all nephron segments in the cortex and outer medulla and is especially pronounced in the medullary thick ascending limb (mTAL). Therefore, the present study was undertaken for examination of the effect of hypothyroidism on the ultrastructure of the rat mTAL. Hypothyroidism was induced by feeding aminotriazole (ATZ), 0.5 g/kg of food, for 4 weeks. A second group of animals received ATZ plus a daily injection of L-thyroxine (T4). A third group was fed a normal diet only and served as control animals. The kidneys were preserved by in vivo perfusion with 3% glutaraldehyde, and tissue from the inner and outer stripe of the outer medulla was processed for electron microscopy. Morphometric analysis revealed a significant decrease in the cross-sectional area of the mTAL in both the inner and outer stripe of the outer medulla in hypothyroid animals. No changes were observed in the surface density of either the apical or basolateral plasma membranes following ATZ treatment. However, when calculated per millimeter tubule, there was a significant decrease in the surface area (SL) of both the apical and basolateral plasma membranes of the mTAL of hypothyroid animals in comparison with control animals. Simultaneous treatment with T4 prevented the ATZ-induced reduction in both tubule cross-sectional area and in the SL of the plasma membrane. These findings suggest that the observed changes in SL of the plasma membrane of the mTAL are due to a regulatory role of thyroid hormone in membrane proliferation as well as in cell growth in general.

Amitrole↗
PubMed1984

Ultrastructure of the thick ascending limb of Henle in the rat kidney.

The thick ascending limb of Henle (TAL) in the rat until recently has been considered a morphologically homogeneous structure despite physiologic and biochemical evidence to the contrary. The present study was designed to examine the ultrastructural characteristics of the TAL in the inner cortex and the outer and inner stripes of the outer medulla using qualitative and quantitative transmission electron microscopy. Kidneys of male Sprague-Dawley rats were preserved by in vivo perfusion with glutaraldehyde for light and electron microscopy. The peritubular diameter and cell height were determined by direct measurements on tubule cross sections. Morphometric analyses were performed on montages of tubule cross sections. The peritubular diameter of the TAL was similar in the three regions under investigation, but the TAL cells were taller in the inner stripe than in the inner cortex and outer stripe. Morphometry revealed significant differences between the three regions with respect to the mean tubular cross-sectional area (AT), the surface density (SV), and the surface area per mm of tubule (ST) of apical and basolateral plasma membranes, and the volume density (VV) of mitochondria. The major morphologic division appeared to be between the inner stripe segment and the remainder of the TAL. These findings document the presence of significant morphologic heterogeneity of the rat TAL.

Animals↗
PubMed1984

Response of intercalated cells of rat outer medullary collecting duct to chronic metabolic acidosis.

The outer medullary collecting duct which is composed of both principal and intercalated cells is involved in hydrogen ion secretion. In the turtle urinary bladder stimulation of hydrogen ion secretion is associated with ultrastructural changes in the mitochondria-rich cells, suggesting that membrane and possibly a proton pump are being transferred from apical tubulovesicular structures and inserted into the apical plasma membrane. Since the intercalated cells resemble the mitochondria-rich cells, this study was initiated to determine whether or not similar changes occur in the outer medullary collecting duct during chronic metabolic acidosis. Rats received ammonium chloride in their drinking water for 15 days and as a daily gavage for 3 days before sacrifice. Control rats received regular tap water. After collection of physiologic data the kidneys were fixed by in vivo perfusion with glutaraldehyde and processed for electron microscopy. No changes were observed in the principal cells. Morphometric analyses of the intercalated cells in both the outer and inner stripe revealed a significant increase in the surface density of the apical plasma membrane concomitant with a striking depletion of the tubulovesicular structures in the apical plasma region of the cell with chronic metabolic acidosis. These findings suggest that in response to chronic metabolic acidosis membrane, possibly containing a proton pump, is transported from the tubulovesicular membrane compartment to the apical plasma membrane of the intercalated cell.

Acidosis↗
PubMed1983

Cellular response to acute respiratory acidosis in rat medullary collecting duct.

The collecting duct of the mammalian kidney is involved in urine acidification. Recent studies in the turtle bladder suggest that hydrogen ion secretion in response to elevated CO2 is regulated by insertion of hydrogen pumps into the luminal membrane of the mitochondria-rich cells. Because intercalated cells of the collecting duct are structurally similar to mitochondria-rich cells of the amphibian bladder, we studied the rat outer medullary collecting duct (OMCD) during respiratory acidosis to determine whether changes compatible with hydrogen ion secretion occur in the intercalated cells. Rats were studied during normal acid-base conditions and after 4-5 h of respiratory acidosis. After collection of physiologic data, the kidneys were fixed by in vivo perfusion and processed for electron microscopy. No changes were observed in the principal cells of the OMCD. Morphometric analysis revealed a significant increase in the surface density of the apical plasma membrane and a decrease in the number of tubulovesicular profiles in the apical region of the intercalated cells throughout the OMCD with respiratory acidosis. There were no changes in surface density of the basolateral membrane. These findings suggest that in response to respiratory acidosis there is transport of membrane from the tubulovesicular membrane compartment to the apical plasma membrane of the intercalated cells.

Acidosis, Respiratory↗
PubMed1983

Kidney structure in hypothyroidism.

Hypothyroidism is associated with changes in renal function and a decrease in kidney weight. The present study was carried out for examination of the effect of the antithyroid drug aminotriazole (ATZ) on kidney structure and especially for determination of whether hypothyroidism affects the whole nephron or only a specific segment of it. Female Sprague-Dawley rats received ATZ in their diet, 0.5 g/kg food for 4 weeks. Control rats received a normal diet. Additional groups of animals receiving ATZ in the diet were given daily injections of L-thyroxine (T4) for determination of whether ATZ-induced changes could be prevented by thyroid hormone. After collection of physiologic data the kidneys were fixed by in vivo perfusion with 3% glutaraldehyde in preparation for light-microscopic morphometry. Following ATZ treatment there was a significant decrease in serum triiodothyronine (T3) and in GFR. Kidney weights were decreased, mainly because of a reduction of cortical tissue. Morphometry showed no changes in the relative volumes of the various compartments of the kidney, indicating that the decrease in weight involved all segments of the nephron. Direct measurements of tubular diameters revealed a decrease in the peritubular diameters in both proximal tubules and the thick ascending limb and a decreased cell height in the thick ascending limb. All the ATZ-induced changes could be prevented by simultaneous treatment with T4, suggesting that the changes were caused by the antithyroid effect of ATZ and were not a nonspecific toxic effect.

Amitrole↗
PubMed1982

Phagocytosis of erythrocytes by the proximal tubule of the rat kidney.

Morphological examination of kidney biopsies from patients with glomerulonephritis and hematuria has revealed the presence of erythrocytes within epithelial cells of the proximal tubule. This observation suggested that the proximal tubule might be capable of phagocytizing morphologically intact erythrocytes. To examine this possibility small quantities of heparinized autologous blood were injected into surface convolutions of proximal tubules of the rat kidney using standard micropuncture techniques. At time intervals ranging from 10 min to 120 h after injection, the kidneys were preserved for light and transmission electron microscopy by drip-fixation with a half-strength Karnovsky's glutaraldehyde-formaldehyde fixative. During the initial 6 h there was a flattening of the brush border and accumulation of electron-dense material representing hemoglobin in apical vacuoles and in lysosome-like structures. From 6 to 15 h after micropuncture, there was progressive loss of the brush border and the simultaneous formation of pseudopodia-like evaginations that extended from the apical plasma membrane and surrounded the individual erythrocytes. By 18 and 24 h, erythrocytes were observed in the proximal tubule cells. At later time intervals, edema, lymphocytic infiltration, and fibrosis were observed in the interstitium. In addition, crystalline structures were present in the lumen and the cells of both proximal and distal tubules. These findings suggest that in addition to their well-established ability to pinocytize hemoglobin and other proteins, the cells of the proximal tubule are capable of phagocytizing morphologically intact autologous erythrocytes. It is possible that phagocytosis by the proximal tubule cells may play a role in the disposal of erythrocytes from the tubular fluid in hematuric conditions.

Animals↗
PubMed1982

Uptake and intracellular distribution of ferritin in the rat distal convoluted tubule.

The purpose of this study was to determine the uptake and intracellular distribution of anionic ferritin (AF) and cationic ferritin (CF) in the distal convoluted tubule (DCT) of the rat kidney. Male Sprague-Dawley rats were prepared for micropuncture, and individual distal tubules were perfused with 5 or 10 mg/ml of AF or 0.1 or 0.5 mg/ml of CF in isotonic saline for either 30 sec or 3 min. The tubules were fixed by perfusion with 6.25% glutaraldehyde either immediately or at different time intervals after exposure to ferritin. Electron microscopy of tubules fixed immediately after perfusion showed no binding of AF to the apical cell membrane, and only traces of AF were observed in small apical structures. In contrast, CF was extensively bound to the apical cell membrane and located in apical vesicles and tubules, and in multivesicular bodies. Occasionally, CF was observed in Golgi vesicles and cisternae. Sixty min after perfusion with ferritin, traces of AF were present in multivesicular bodies and lysosome-like structures. Thirty and 60 min after perfusion, large concentrations of CF were located in multivesicular bodies and lysosome-like bodies. This study reveals that in the DCT, CF is bound to the apical cell membrane and taken up into the tubule cells, whereas only traces of AF are taken up, indicating that the charge of a protein molecule may determine whether or not the protein is reabsorbed by the DCT. The demonstration of CF in the Golgi complex is compatible with the existence of membrane recycling in cells of the DCT.

Animals↗
PubMed1980

Mercury accumulation in kidney lysosomes or proteinuric rats.

The purpose of the present study was to determine whether lysosomal accumulation of mercury in the kidney is due to a leakage of protein-bound mercury through the glomerular filtration barrier followed by reabsorption into the lysosomal system of the proximal tubule. The subcellular distribution of mercury in the kidney was studied in four different groups of rats with and without proteinuria: normal young rats, young rats with aminonucleoside nephrosis, old rats with spontaneous proteinuria, and old rats with chronic mercury intoxication and proteinuria. Radioactive mercuric chloride (203HgCl2) was injected s.c. into the rats 72 hours before sacrifice. Cell fractionation experiments were carried out on homogenates of the renal cortex by differential centrifugation. Determination of radioactive mercury in the subcellular fractions revealed that mercury was concentrated in the lysosomal fraction of all rats with proteinuria. In contrast, normal rats without proteinuria had the highest concentration of mercury in the supernatant, and there was no enrichment of mercury in the lysosomal fraction. Gel filtration chromatography performed on urine samples from proteinuric rats demonstrated that excreted mercury in renal lysosomes of proteinuric urine support the hypothesis that mercury bound to plasma proteins passes the glomerular filtration barrier in proteinuric conditions and enters the lysosomal system of the proximal tubule by way of endocytosis.

Albumins↗
PubMed1978

Effects of mercury on lysosomal protein digestion in the kidney proximal tubule.

The effect of mercury on renal lysosomal protein digestion was studied after administration of mercury in vitro and in vivo. Mercuric chloride or methylmercury chloride was added in vitro to lysosomal enzymes isolated from normal rats, and subsequently, digestion experiments were carried out using 125I-labeled lysozyme or cytochrome c as substrate proteins. Both mercury compounds produced a concentration-dependent inhibition of the degradation of the proteins, mercuric chloride being the strongest inhibitor. Mercuric chloride was also administered to rats in vivo for 5 to 8 months. Renal lysosomal enzymes from these animals also had a decreased ability to digest for the two substrate proteins. Furthermore, the digestion of lysozyme intravenously injected into mercury-intoxicated rats was decreased in renal cortical slices incubated in vitro. Electron microscope autoradiography showed that intravenously injected labeled lysozyme was located primarily over lysosomes in proximal tubule cells 1 hour after injection in both control animals and mercury-intoxicated rats. These results suggest a decreased catabolism of low molecular weight proteins in the kidney during chronic mercury intoxication.

Animals↗
PubMedDate not supplied

Influence of ET(B) receptor antagonism on pregnancy outcome in rats.

OBJECTIVE: To determine the effect of endothelin-B (ET(B))-selective receptor antagonism on pregnancy outcome in normal rats. METHODS: ET(B) receptor antagonist (A-192621; 5.0, 10.0, and 15.0 mg/kg per day) or vehicle was infused subcutaneously for 7 days by osmotic pump. Infusion was begun on day 14 of a 22-day gestation. Nonpregnant animals were treated similarly, and blood pressure (BP) responses and plasma antagonist levels were compared to those in pregnant animals. Mean arterial pressure (MAP) was measured on days 1, 4, and 7 of the infusion. Plasma ET(B) antagonist levels were measured on day 7 of infusion. On gestational day 21, fetal and placental weights and viability were evaluated at hysterotomy. Data were analyzed by analysis of variance and are presented as mean +/- standard error of the mean. RESULTS: Fetal and placental weights were significantly lower at doses of 10 and 15 mg/kg per day of the ET(B) antagonist compared with vehicle-treated controls (P <.001); these effects were less severe at 15 than at 10 mg/kg per day despite a fourfold higher plasma level of antagonist. Mean arterial pressure was significantly higher at 10 and 15 mg/kg per day compared with controls, but only on infusion day 1 (P <.05). In contrast, MAPs for nonpregnant rats were elevated throughout the infusion at all doses of the ET(B) antagonist (P <.05). CONCLUSIONS: ET(B) receptor antagonism inhibited fetal growth and increased maternal MAP in a dose-dependent manner, although the effect on BP was not sustained in pregnant animals. ET(B) receptor antagonism is detrimental to pregnancy outcome in the rat.

Abortion, Spontaneous↗