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Biomedical subjects

E Ritz

Publications and source records attributed to E Ritz.

At least 451 records · Page 25Linked to original sources
PubMed1993

Growth hormone-induced glomerular hyperfiltration is dependent on vasodilating prostanoids.

Exogenous growth hormone (GH) and insulin-like growth factor (IGF)-I induce an increase of renal hemodynamics in normal subjects, but the precise mechanism mediating this phenomenon has not been explored in humans. We investigated whether the renal response to exogenous GH requires the presence of vasodilating prostaglandins (PG). In 10 healthy normotensive women with normal renal function, the effect of recombinant human (rh)GH on glomerular filtration rate (GFR) was examined using an intraindividual cross-over design. The subjects were studied under conditions of normal hydration and controlled sodium and protein intake without and with coadministration of indomethacin, 150 mg/d. rhGH, 4.5 IU twice per day, was administered by subcutaneous self-injection for 3 days. GFR was measured as inulin clearance (Cin) in the morning hours in the fasting state in supine position before and after 3 days of rhGH treatment. Baseline GFR was 115.7 +/- 10.1 (SD) mL/min/1.73 m2. Three days of treatment with rhGH caused a 50% increase in serum IGF-I values and GFR increased by 10% to 127.9 +/- 11.7 mL/min/1.73 m2 (P < 0.03). The study was repeated under coadministration of indomethacin, which was started 2 days before application of rhGH. Despite a similar increase in serum IGF-I values, the increase in GFR was completely blocked by indomethacin. Urinary PGE2 excretion was not stimulated by rhGH, but decreased by 50% during indomethacin treatment, as expected. These findings suggest that the increase of GFR during GH treatment in humans is mediated by or requires the presence of vasodilating prostanoids.

Adult↗
PubMed1993

Intermittent and continuous exposure to 1,25(OH)2D3 have different effects on growth plate chondrocytes in vitro.

Intermittent 1,25(OH)2D3 administration is widely used to suppress parathyroid glands in secondary (renal) hyperparathyroidism. It is unknown whether the effects of continuous and intermittent 1,25(OH)2D3 differ on vitamin D target organs other than parathyroids. Using primary cultures of rat chondrocytes (tibia) we compared the effects of continuous versus intermittent exposure to physiologic concentrations of 1 alpha,25(OH)2D3 on proliferation (radiothymidine incorporation), cell count, protein synthesis ([3H]-leucine incorporation), alkaline phosphatase activity (as a marker of differentiation) and 1 alpha,25(OH)2D3 receptor (VDR) regulation. Cells were synchronized and then exposed for variable periods to a medium containing 10% delipidated FCS and 10(-8) M to 10(-12) M 1 alpha,25(OH)2D3 (or 1 beta,25(OH)2D3 as specificity control). Intermittent (8 hr exposure every 48 hr) as well as continuous (sham washing) administration of 1 alpha,25(OH)2D3 had a biphasic effect on proliferation, that is, stimulation at low (10(-12) M) and inhibition at high (10(-8) M) concentrations. At 10(-12) M intermittent 1 alpha,25(OH)2D3 yielded higher cell counts than continuous 1,25(OH)2D3. This was seen in the log phase, which was day 3 (continuous 141 +/- 2.3% of solvent control; intermittent 185 +/- 2.0%) and in the plateau phase of growth, which was day 6 (128 +/- 2.6 vs. 169 +/- 2.7% of solvent control). Dependence on extracellular Ca is suggested by the effects of varying nominal Ca concentrations in the medium and of Ca channel blockers. Even two hours of exposure to 1 alpha,25(OH)2D3 (10(-12) M) yielded maximal activation of AP during postincubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1993

Effects of rhGH and rhIGF-1 on renal growth and morphology.

It is known that in rodents recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor (rhIGF-1) increase renal mass. It is uncertain, however, whether renal mass increases in proportion to body growth, or whether renal growth is stimulated selectively. In 120 to 150 g female Sprague-Dawley rats, we measured the effects of rhGH and rhIGF-1 and their combination by the following parameters: kidney weight/body weight ratio, DNA/protein ratio, mRNA of GH receptor and of IGF-1, mitosis index and PCNA (by immunohistology), zonal architecture and glomerular diameter by micromorphometry. Both rhGH and rhIGF-1 dose-dependently increased renal weight and body weight over vehicle treated controls. With rhGH, liver dry weight/body weight ratio increased, but kidney dry weight/body weight ratio remained unchanged (0.99 +/- 0.06 x 10(-3) vs. 1.02 +/- 0.07 in vehicle controls). In contrast, a significant increase of kidney dry weight/body weight ratio was seen in rats treated with rhIGF-1 (1.3 +/- 0.21 x 10(-3). Addition of high doses of rhGH to high doses of rhIGF-1 caused no further increase of the ratio despite a significant further increase of body weight. rhGH increased the abundance of renal GH receptor mRNA (0.46 +/- 0.32 amol/microgram DNA vs. 0.08 +/- 0.07 in controls) and of IGF-1 mRNA (1.35 +/- 0.5 pg/micrograms DNA vs. 0.35 +/- 0.17), whereas no change was seen with IGF-1 treatment. rhGH and rhIGF-1 increased kidney DNA/protein ratio, mitoses and PCNA expression in various renal structures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Intermittent versus continuous administration of 1,25-dihydroxyvitamin D3 in experimental renal hyperparathyroidism.

Conflicting results have been reported regarding the efficacy of intermittent versus continuous administration of 1,25(OH)2D3 in renal secondary hyperparathyroidism. To address this issue we examined sham-operated control rats and hyperparathyroid rats with subtotal (5/6) nephrectomy (Nx). The Nx animals (20 to 22 animals per group) were subjected to three treatment protocols: (i) solvent treatment (Nx-solvent); (ii) two i.p. injections of 35 pmol 1,25(OH)2D3 on days 0 and 4 (Nx-bolus); and (iii) continuous infusion of 70 pmol 1,25(OH)2D3 over six days via osmotic minipump (Nx-infusion). All measurements were performed six days after start of treatment. As compared to sham-operated controls, the pre-pro-PTH/beta-actin mRNA ratio was 2.04-fold higher in Nx-solvent. Both modes of administration of 1,25(OH)2D3 resulted in inhibition of PTH mRNA concentrations relative to Nx-solvent. The pre-pro-PTH/beta-actin mRNA ratio was, however, significantly lower (P < 0.05) in Nx-bolus than in Nx-infusion (Nx-bolus 1.26 higher than sham-operated controls; Nx-infusion 1.65 higher than sham-operated controls). Aminoterminal PTH (N-PTH) serum concentrations were higher in Nx-solvent (52 +/- 4 pg/ml) than in sham-operated controls (32 +/- 3 pg/ml, P < 0.01). N-PTH concentrations in Nx-bolus (38 +/- 4 pg/ml) were significantly lower than in Nx-solvent (P < 0.01) and in Nx-infusion (46 +/- 4 pg/ml, P < 0.05). Parathyroid gland weight (microgram/g body wt) was higher in Nx-solvent (1.30 +/- 0.08 pg/ml) than in sham-operated controls (0.79 +/- 0.04 pg/ml, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

In situ production of TNF-alpha, IL-1 beta and IL-2R in ANCA-positive glomerulonephritis.

Humoral and cellular immune mechanisms are thought to be involved in various forms of vasculitis and glomerulonephritis. Recent clinical and experimental results point to a role of cytokines in ANCA-positive vasculitides. We analyzed tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-2 receptors (IL-2R) in renal biopsies and in plasma from 22 patients with Wegener's granulomatosis and microscopic polyangiitis. Kidney biopsies were examined by immunocytochemistry, polymerase chain reaction and in situ hybridization. Immunoreactive TNF-alpha, IL-1 beta and/or IL-2R positive infiltrating cells were observed in 21 of 22 biopsies. TNF-alpha, IL-1 beta and IL-2R staining was evident in the interstitium and at periglomerular and perivascular sites. The number of positive cells was markedly increased in biopsies with active lesions. Positive cells were also present in cellular and fibrocellular crescents, surrounding tuft necrosis and in the walls of arteries and arterioles with acute vasculitic lesion. Some tubular epithelial cells stained for TNF-alpha and IL-1 beta. TNF-alpha, IL-1 beta and IL-2R positive infiltrating cells correlated with the presence of histologically active renal lesions. The evaluation of TNF-alpha and IL-1 beta expression at the mRNA level assessed by the polymerase chain reaction demonstrated specific transcripts for TNF-alpha and IL-1 beta in all six cases analyzed. In situ hybridization studies showed an increased expression of mRNA for TNF-alpha and IL-1 beta in infiltrating mononuclear cells, in epithelial cells of Bowman's capsule and in some tubules, predominantly of patients with active renal lesions. The results at the mRNA level correlated with the immunocytochemical findings. Compared to healthy individuals higher TNF-alpha plasma levels were observed in patients with vasculitis (34.4 +/- 16.6 pg/ml (SEM) vs. 1.9 +/- 0.7 pg/ml in controls; P < 0.01). All patients presented a marked increase in sIL-2R plasma levels (3512 +/- 485 U/ml vs. 397 +/- 21 U/ml in healthy controls; P < 0.001). IL-1 beta was not detected in most plasma samples. Elevated TNF-alpha and sIL-2R plasma levels were related to active renal lesions. Our study clearly demonstrates that in ANCA-positive vasculitis TNF-alpha and IL-1 beta are produced in situ by activated infiltrating mononuclear cells and resident renal cells. Intrarenal localization of cytokine producing cells and the correlation between cytokine production and histological signs of activity suggest that TNF-alpha and IL-1 beta are important locally acting mediators in the vasculitic/glomerulonephritic process.

Adolescent↗
PubMed1993

Pathophysiology of hypertensive renal damage.

The kidney may contribute to and be damaged by hypertension. Evidence from studies of renal transplant recipients and familial studies suggests a genetic component for the occurrence of hypertension and nephrosclerosis. Glomerular injury may result from glomerular hypertension caused by loss of autoregulation and afferent renal vasodilatation. Glomerular injury may be mediated by injury to endothelial cells, which, having lost their thromboresistance, may initiate intravascular coagulation and alter the balance between endothelin and endothelium-derived relaxing factor. Increased transit of protein-laden fluid into the mesangial space also may mediate hypertensive nephrosclerosis. Several studies have provided encouraging evidence that antihypertensive therapy, particularly with angiotensin-converting enzyme inhibitors or calcium antagonists, can slow the progression of renal damage.

Animals↗
PubMed1993

Polymorphism of the angiotensin I converting enzyme gene is apparently not related to high blood pressure: Dutch Hypertension and Offspring Study.

OBJECTIVE: Studies in genetically hypertensive rats and their normotensive Wistar-Kyoto control rats have revealed a linkage of a chromosomal region containing the angiotensin converting enzyme (ACE) gene with blood pressure. This led to the hypothesis that ACE is a possible candidate gene for primary hypertension in humans. We defined the genotypes and allele frequencies of an insertion-deletion (I/D) polymorphism in parental couples who both had either high or low blood pressure and in their offspring. SUBJECTS: Parents (n = 111) and offspring (n = 75) with defined blood pressure status from the Dutch Hypertension and Offspring Study. METHODS: Genomic DNA was amplified by polymerase chain reaction using primers flanking the polymorphic region in intron 16 of the ACE gene. Alleles were detected on agarose gels stained with ethidium bromide. RESULTS: Allele frequencies for the D-allele were similar in parents with high (0.66) and low blood pressure (0.59) and in their offspring (0.67 and 0.69, respectively). A similar lack of difference was found with respect to the complementary I-allele. CONCLUSIONS: In the present rather large sample we failed to find a significant association between I/D polymorphism of the ACE gene and blood pressure status in subjects with high or low blood pressure and in their offspring.

Adult↗
PubMed1993

The effect of enalapril on glomerular growth and glomerular lesions after subtotal nephrectomy in the rat: a stereological analysis.

INTRODUCTION: Angiotensin converting enzyme (ACE) inhibitors have a beneficial effect on glomerular injury in different models of renal damage. Their presumed nephroprotective action has been related partly to actions on glomerular growth. We examined the effect of prophylactic administration of a moderate dose of enalapril (50 mg/l in drinking water) in male Sprague-Dawley rats on a diet containing 40% protein and moderate NaCl. METHODS: The rats were followed for 8 weeks after subtotal nephrectomy and compared with sham-operated matched controls. RESULTS: The number of glomeruli per kidney was reduced significantly in both the enalapril-treated and control groups. The median glomerulosclerosis index was significantly lower in the enalapril-treated than in the untreated subtotally nephrectomized rats. The mean absolute glomerular volume was significantly higher after subtotal nephrectomy, but was significantly lower in the enalapril-treated than in the untreated subtotally nephrectomized rats. The total numbers of cells per glomerulus and of mesangial or endothelial cells, as well as nuclear volumes of mesangial cells and the total capillary length per glomerulus, were all significantly higher after subtotal nephrectomy. These parameters were significantly lower in the enalapril-treated than in the untreated nephrectomized rats. The rise in systemic blood pressure was modest in the nephrectomized rats and the arteriolar volume: length ratio was unchanged by treatment with enalapril. CONCLUSIONS: In subtotally nephrectomized rats enalapril inhibits (but fails to reverse completely) the compensatory glomerular enlargement and the increase in mesangial cell number and activation, with a concomitant reduction in the development of glomerulosclerosis. The results is compatible with antiproliferative, and possibly antiangiogenic, actions of ACE inhibitors.

Animals↗
PubMed1993

Angiotensin II enhances insulin sensitivity in healthy volunteers under euglycemic conditions.

OBJECTIVE: It has been postulated that vasoconstrictors cause insulin resistance. This effect has been documented for epinephrine but not for angiotensin II (Ang II). The aim of this study was to investigate the effect of the latter on insulin sensitivity. DESIGN: In order to study the influence of subpressor doses of Ang II on insulin-mediated glucose uptake under euglycemic conditions, eight healthy volunteers were allocated in random order to sham infusion or infusion of Ang II (first 0.75 ng/kg per min and subsequently 1.5 ng/kg per min). In addition, in seven of the subjects Ang II was infused after 3 days of indomethacin pretreatment (150 mg/day). METHODS: Insulin-mediated glucose uptake (expressed as M value) was measured with the euglycemic clamp technique. Insulin levels were measured enzymatically, plasma renin activity, Ang II, aldosterone and C-peptide levels by radioimmunoassay, blood pressure by Dinamap and muscle blood flow by plethysmography. RESULTS: The M value after sham infusion was 7.81 +/- 1.52 mg/kg per min and after 1.5 ng/kg Ang II per min was 9.76 +/- 1.26 mg/kg per min (P < 0.001). Indomethacin pretreatment did not abolish the Ang II-induced rise in the M value. Mean arterial blood pressure during the euglycemic clamp was unchanged with sham infusion and the low dose of Ang II. It increased slightly with the higher dose of Ang II. Inferior limb muscle perfusion was higher after infusion of Ang II than after sham infusion; this effect was not obliterated by indomethacin pretreatment. CONCLUSIONS: Ang II increases insulin-mediated glucose uptake: that is, it enhances insulin sensitivity by mechanisms independent of prostaglandins. The observations are of potential relevance to the changes in insulin sensitivity in some forms of hypertension.

Adult↗
PubMed1993

Chronic lead exposure in rats: effects on blood pressure.

The influence of Pb exposure on blood pressure was investigated in Wistar Kyoto, Sprague Dawley and stroke prone spontaneously hypertensive rats. In short-term experiments, a dose-dependent decrease of blood pressure was found with administration of Pb acetate in drinking fluid. This effect was more pronounced in young, male as compared to old, female animals. Pressor responses to noradrenaline and ANG II were decreased. In contrast, long-term Pb exposure of more than 1 year duration consistently caused hypertension. In SHR-sp a high proportion of animals died from cerebrovascular haemorrhage even before developing hypertension. Chronically Pb exposed hypertensive rats had increased plasma volume and total body sodium despite normal renal function. Plasma concentrations of catecholamines and PRA were normal. The results show a biphasic effect of Pb on blood pressure. An important role of renal sodium retention in chronic Pb-induced experimental hypertension is suggested.

Age Factors↗
PubMed1993

Autosomal dominant polycystic kidney disease (ADPKD)--mechanisms of cyst formation and renal failure.

None of the hypotheses proposed so far to explain cyst formation in autosomal dominant polycystic kidney disease (ADPKD) is entirely satisfactory, e.g. the theory of tubular obstruction by intraluminal polyps or dilatation of nephron segments as a consequence of abnormal compliance of the basement membrane. Recent in vitro studies show that (i) synthesis of basement membrane material is abnormal and that (ii) the direction of transepithelial resorptive flux into a secretory mode is reversed as a consequence of faulty insertion of Na, K-ATP'ase into the luminal membrane. It remains unclear why cystic transformation of a few percent of nephrons should cause endstage renal failure. Our clinical and experimental studies do not provide evidence to support some hypotheses proposed in the past, i.e. that renal parenchyma is compressed by expanding cysts and that glomeruli are overperfused. Our histological studies show that progression to endstage renal failure is associated with (i) progressive arteriolar lesions (out of proportion to the vascular lesions seen in extrarenal vascular beds; and (ii) progressive interstitial fibrosis. It appears that fibroblasts in ADPKD are particularly sensitive to platelet derived growth factor (PDGF) which is secreted by epithelial cells of the cyst wall in a paracrine fashion. In contrast to previous opinion, which was presumably skewed by ascertainment bias, it appears that not all, and perhaps not even a majority, of ADPKD patients progress to endstage renal failure. Factors related to progression are gender, family history and hypertension. Both abnormal sodium excretion and inappropriate renin secretion play a role in the genesis of hypertension. Elevated blood pressure, albeit within the normotensive range, is demonstrable even in prepubertal children. The involvement of renin in renal vasoconstriction of normotensive ADPKD patients suggests a particular role of ACE inhibitors in the management of these patients.

Dilatation, Pathologic↗
PubMed1993

Serum lipids predict cardiac death in diabetic patients on maintenance hemodialysis. Results of a prospective study. The German Study Group Diabetes and Uremia.

The objective of this study was to measure cholesterol concentrations in diabetic patients at the beginning of maintenance hemodialysis treatment and to define their role as predictors of subsequent cardiac death on maintenance hemodialysis. The design of this study consisted of a prospective study of all consecutive diabetic patients newly admitted to 28 German dialysis centers between January 1985 and October 1987. The patients were examined on admission and subsequently followed for 45 months on dialysis. This study included 196 patients, 67 type I (43 male, 24 female, median age 49 years, range 22-73) and 129 type II (54 male, 75 female, aged 64 years, range 37-82). Lipids (total cholesterol, triglycerides low-density lipoprotein (LDL) cholesterol high-density lipoprotein (HDL) cholesterol apolipoprotein B and A and anthropometric indices (body mass index, triceps skinfold thickness) were measured. The outcome was death, i.e., cardiovascular (myocardial infarction, sudden death, other cardiac causes, stroke) and noncardiovascular death during a 45-month follow-up. At the start of treatment, total cholesterol, triglycerides LDL cholesterol, LDL/HDL ratio and apolipoprotein B were significantly higher in diabetics than in healthy controls or patients with standard primary renal disease starting dialysis. Only minor differences were found between males and females and type I and type II diabetics. Fourty-three percent of type I and 50% of type II diabetics died, 61% from cardiovascular causes, mostly myocardial infarction (in 40% reinfarction) and sudden death. On admission, diabetics subsequently dying from myocardial infarction had significantly higher median cholesterol than survivors, i.e., 259 versus 222 mg/dl, and higher LDL cholesterol, LDL/HDL ratio and apolipoprotein B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Renal functional reserve in healthy elderly subjects.

The increase in GFR after an amino acid (AA) load, the so-called renal functional reserve, is impaired in the aged rat. Whether the renal functional reserve predicts the progression of renal disease in humans is controversial, but it is possible that age-related alterations of renal hemodynamics are relevant for the evolution of renal disease in the elderly. We compared renal hemodynamics before and after an AA infusion in 15 healthy normotensive subjects of young age (seven women, eight men; median age, 26 yr; range, 23 to 32) and in 10 subjects of old age (six women, four men; median age, 70 yr; range, 61 to 82) on normal dietary protein intake. Baseline GFR and effective RPF were measured after 12 h of fasting by the inulin (Cin) and para-aminohippurate (Cpah) steady-state infusion techniques. The renal functional reserve was examined after an overnight AA infusion (7% solution; 83 mL/h). Median basal Cin and Cpah were significantly lower (P < 0.01) in the elderly (102 and 339 mL/min per 1.73 m2) than in the young subjects (122 and 647 mL/min per 1.73 m2), but virtually all GFR values of the elderly were still within the normal range. Median Cin upon infusion of AA was 118 mL/min per 1.73 m2 (range, 98 to 137) in the elderly and 146 (range, 120 to 171) in the young, respectively. Corresponding values of Cpah were 349 mL/min per 1.73 m2 in the elderly versus 689 mL/min per 1.73 m2 in the young. Cin increased significantly (P < 0.01) after the AA load in both young and elderly subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Elevated blood pressure profile and left ventricular mass in children and young adults with autosomal dominant polycystic kidney disease.

Twelve children (< 15 yr) and 12 young adults with autosomal dominant polycystic kidney disease (ADPKD) confirmed by ultrasonography and 24 nonaffected individuals matched for age, sex, and body surface area were examined with ambulatory blood pressure monitoring and echocardiography. All patients and controls had normal renal function (median serum creatinine, 0.85 mg/dL; range, 0.5 to 1.1). In children, daytime and nighttime blood pressures were not significantly different from those of controls; the median left ventricular mass index (in grams per square meter) was higher in patients (66.6 g/m2) than in controls (61.3 g/m2; P < 0.002), although all values remained within the normal range. In young adults with ADPKD, mean arterial blood pressure was significantly higher than that in controls both during daytime (98.3 mm Hg; range, 74 to 126 versus 90.6 mm Hg; range, 73 to 116; P < 0.006) and during nighttime (83.2 mm Hg; range, 66.5 to 125 versus 79.0 mm Hg; range, 63 to 91; P < 0.05). In parallel, the median left ventricular mass index was significantly higher in young adults (81.8 g/m2; range, 62 to 174 versus 64.3 g/m2; range, 52 to 102; P < 0.02). The results document that ambulatory daytime and nighttime blood pressures and left ventricular mass indices are higher in asymptomatic carriers of the ADPKD trait compared with controls, although most values are still within the normal range.

Adolescent↗