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Eberhard Ritz

Publications and source records attributed to Eberhard Ritz.

At least 19 recordsLinked to original sources
PubMed2004

Retinoic acid receptor alpha and retinoid X receptor specific agonists reduce renal injury in established chronic glomerulonephritis of the rat.

Retinoids, derivatives of vitamin A, inhibit mesangial cell proliferation, glomerular inflammation, and extracellular matrix deposition in acute anti-Thy1.1 glomerulonephritis (Thy-GN) of the rat. We examined a model, chronic mesangioproliferative Thy-GN (MoAb 1-22-3), which is more akin to human disease. Treatment started on day 23 when Thy-GN had already been established. Nonnephritic control and Thy-GN rats were treated orally for 67 days with vehicle or with two doses of either the retinoic acid receptor alpha-specific agonist AGN 195183 (RARalpha agonist) or the retinoid X receptor specific agonist AGN 194204 (RXR agonist). Doses of either the RARalpha or the RXR agonist significantly reduced albuminuria and normalized blood pressure during the course of treatment. The glomerulosclerosis index, glomerular cell and interstitial cell counts, and area of the interstitial space were significantly lower in nephritic rats treated with the RARalpha agonist or RXR agonist than with vehicle. The RARalpha and RXR agonist significantly reduced the infiltration of the glomerulus by macrophages. The increase in glomerular TGFbeta1 and prepro-ET(1) gene expression in vehicle-treated nephritic rats was significantly attenuated by RARalpha or RXR agonists. Glomerular expression of RXRalpha and RARalpha receptor mRNA was significantly greater in vehicle-treated nephritic rats than in nonnephritic controls. Treatment with RARalpha or RXR agonists tended to normalize retinoid-receptor gene expression. Our data indicate that both RARalpha agonists and RXR agonists reduce renal damage in rats with established chronic glomerulonephritis. Receptor-specific retinoids may provide a novel therapeutic approach for the treatment of chronic glomerulonephritis.

Albuminuria↗
PubMed2004

No aggravation of renal injury in apolipoprotein E knockout mice (ApoE(-/-)) after subtotal nephrectomy.

BACKGROUND: There is substantial experimental evidence that various forms of dyslipidaemia aggravate the course of renal failure and that reversal of dyslipidaemia ameliorates progression of renal failure. The apolipoprotein E knockout mouse (ApoE(-/-)) is an established model of accelerated atherogenesis. We investigated whether the course of renal disease after uninephrectomy (UNX) and subtotal nephrectomy (SNX) is altered in ApoE(-/-) mice compared with their genetic controls. METHODS: Ten-week-old, male ApoE(-/-) mice (body weight 25+/-2 g) were subjected either to sham operation (sham), UNX or SNX. C57BL/6 sham, UNX and SNX mice served as controls (body weight 26+/-3 g). The food intake of ApoE(-/-) and C57BL/6 mice was kept identical by a pair-feeding protocol. After 12 weeks, mean arterial blood pressure and heart rate were measured in awake resting mice, the kidneys were perfusion fixed and analysed using quantitative histological methods, immunohistochemistry and RT-PCR. RESULTS: At baseline, the sham ApoE(-/-) mice had significantly higher (P<0.05) serum cholesterol and triglycerides than the controls. In parallel, mean arterial blood pressure was significantly elevated in sham ApoE(-/-) mice compared with controls (137+/-15 vs 116+/-4 mmHg; P<0.05). In the sham groups, the glomerulosclerosis index was significantly higher in the ApoE(-/-) mice (1.05+/-0.14 vs 0.57+/-0.07; P<0.05), whereas the tubulointerstitial damage score was comparable (0.06+/-0.04 vs 0.04+/-0.02; n.s.). After SNX there was a significant increase in glomerulosclerosis index, but no difference could be detected between ApoE(-/-) and controls (1.75+/-0.16 vs 1.61+/-0.01, n.s.). The same was true for the tubulointerstitial damage index. CONCLUSIONS: Despite some glomerulosclerosis and elevated mean arterial blood pressure at baseline, no acceleration of progression of renal disease was found in this genetic model of hyperlipoproteinaemia. This observation suggests that despite the known spontaneous histological changes in untouched kidneys, however, the presence of hyperlipidaemia in the ApoE(-/-) mouse does not cause more severe progression in the present models of moderate renal disease.

Animals↗
PubMed2004

Beneficial Effects of Estrogens on Indices of Renal Damage in Uninephrectomized SHRsp Rats.

Renal diseases tend to be less severe among premenopausal female patients, compared with male patients. Experimental data on the effects of estrogens on renal damage are controversial, and potential underlying mechanisms have not been fully clarified. Three-month-old, female, uninephrectomized (UNX), sham-operated or ovariectomized (OVX) SHRsp rats were left untreated or received either 17beta-estradiol 3-benzoate (25 micro g/d) or estriol (0.02 mg/d) daily. After 3 mo, indices of renal damage (glomerulosclerosis index and tubulointerstitial damage index) and glomerular geometric parameters were investigated. The expression of desmin, TGF-beta, endothelin-1, collagen IV, endothelial nitric oxide synthase, and estrogen receptors alpha and beta in the glomeruli and tubulointerstitium was immunohistochemically evaluated. Estradiol and estriol did not significantly affect kidney weights or BP. Estradiol and estriol caused significant reductions in albuminuria (vehicle-treated UNX/OVX animals, 25.4 +/- 8.52 mg/24 h; estradiol-treated UNX/OVX animals, 15.37 +/- 6.12 mg/24 h; estriol-treated UNX/OVX animals, 6.54 +/- 2.24 mg/24 h). The glomerulosclerosis index was significantly lower in estriol- and estradiol-treated animals (estradiol-treated UNX/OVX animals, 0.69 +/- 0.16; estriol-treated UNX/OVX animals, 0.21 +/- 0.12; P < 0.05), compared with vehicle-treated animals (1.46 +/- 0.09); the tubulointerstitial damage index exhibited a similar pattern. The mean glomerular volume was significantly less in estrogen-treated animals. UNX/OVX animals demonstrated significantly greater expression of TGF-beta and endothelin-1 in immunohistochemical, in situ hybridization, and reverse transcription-PCR assays. This increase was abrogated by estriol but not estradiol. Similarly, significantly higher glomerular and tubulointerstitial expression of proliferating cell nuclear antigen and collagen IV was observed in UNX/OVX animals, and expression was decreased by estriol but not estradiol. It was concluded that, in the UNX model of spontaneous renal damage, glomerular lesions and glomerular hypertrophy were reduced by estriol but less consistently by estradiol. In parallel, loss of podocytes, evidence of podocyte injury (i.e., desmin expression), and expression of mediator systems of glomerular damage were decreased, pointing to a major renoprotective action of estriol.

Animals↗
PubMed2004

Atherosclerosis in dialyzed patients.

In the recent HEMO study, the most common cause of death in dialyzed patients was ischemic heart disease. In Europe there are regional differences, but the mortality due to cardiovascular disease is also very high. The long-lasting controversy whether the high incidence and prevalence of atherosclerotic manifestations (particularly ischemic heart disease) may be explained by known risk factors, or non-traditional risk factors are also involved seems to be partially solved with the increasing evidence that the latter hypothesis is true. Thus, together with classic risk factors such as hypertension, dyslipidemia and diabetes, other situations such as microinflammation, increased concentration of asymmetrical dimethyl-L-arginine, disturbed phosphate metabolism and anemia may represent important risk factors for accelerated atherosclerosis in dialyzed patients.

Anemia↗
PubMed2003

1,25-Dihydroxyvitamin D3 decreases podocyte loss and podocyte hypertrophy in the subtotally nephrectomized rat.

1,25(OH)(2)D(3) has antiproliferative effects and promotes cell differentiation. This consideration has provided the rationale for studies in subtotally nephrectomized rats showing that 1,25(OH)(2)D(3) interfered with glomerulosclerosis. The cellular mechanisms involved have remained obscure, however. It was the purpose of the present study to assess glomerular structure and cellular composition in subtotally nephrectomized (SNX) rats treated with nonpharmacological doses of 1,25(OH)(2)D(3). Male Sprague-Dawley rats were sham operated (sham) or underwent SNX under general anesthesia and received either solvent or 1,25(OH)(2)D(3) (3 ng.100 g body wt(-1).day(-1) sc). Blood pressure (BP) and albuminuria were measured. After 16 wk, the remnant renal tissue was perfusion fixed and morphometric and stereological measurements were carried out. The expression of proliferating cellular antigen (PCNA), cyclin-dependent kinase inhibitor p27, Wilms tumor gene (WT1), and desmin, a marker of early podocyte damage, was investigated by immunohistology. BP, serum creatinine, and urinary albumin excretion were significantly higher in SNX than in sham rats. Albuminuria was significantly lower in SNX+1,25(OH)(2)D(3) compared with SNX+solvent rats. Mean glomerular tuft volume was significantly higher in SNX+solvent (2.69 +/- 0.21 gx 10(6) microm(3)) than in sham rats (1.44 +/- 0.17 and 1.28 +/- 0.14 x 10(6) microm(3)); it was significantly (P < 0.05) lower in SNX+1,25(OH)(2)D(3) rats (1.81 +/- 0.16 x 10(6) microm(3)). The main finding was a significantly higher number of podocytes in SNX+1,25(OH)(2)D(3) (88 +/- 9) and sham (98 +/- 17) compared with SNX+solvent rats (81 +/- 8.7). In parallel, the increase in podocyte volume in SNX+solvent rats was abrogated by treatment with 1,25(OH)(2)D(3), and immunohistochemistry revealed less expression of desmin, PCNA, and p27, suggesting less podocyte injury and activation of the cyclin cascade. This study identifies the podocyte as an important target cell for the renoprotective action of 1,25(OH)(2)D(3). This notion is suggested by less evidence of podocyte injury, decreased podocytes loss, and abrogation of podocyte hypertrophy, findings that may also explain less pronounced albuminuria and glomerulosclerosis.

Animals↗
PubMed2003

The renal retinoid system: time-dependent activation in experimental glomerulonephritis.

Retinoids reduce renal damage in rat experimental glomerulonephritis. It is unknown, however, how local and systemic retinoid pathways respond to renal injury. We used a rat model of artificially induced acute anti-Thy1.1-nephritis (THY-GN). We examined the extrarenal and glomerular expression of the retinol (RoDH) and retinal (RalDH) dehydrogenases 1 and 2 as well as the expression of the retinoic acid (RAR) and retinoid X (RXR) receptor subtypes alpha, beta, and gamma. Furthermore, we investigated serum and glomerular retinoid concentration patterns. On days 3, 7, and 14, we compared nonnephritic rats (control group; CON) to THY-GN rats with respect to systolic blood pressure and glomerular cell count per cross section. Systolic blood pressure and glomerular cell count were significantly higher in THY-GN rats on days 7 and 14 (P < 0.001). We found a 60% reduction in expression levels for retinoid receptors and dehydrogenases in nephritic glomeruli on day 3, but a threefold increase on day 7 (P < 0.001 vs. CON). The same applies to RAR alpha protein. Hepatic expression of retinoid receptors was not influenced. On day 14, glomerular expression levels for retinoid receptors and retinoid-metabolizing enzymes had returned to a normal level, glomerular cell count being still increased. Administering 13-cis retinoic acid (isotretinoin) lowered blood pressure and glomerular cell count in nephritic rats but failed to influence the glomerular expression of retinoid receptors or retinoid-metabolizing enzymes. Our data document a stimulation of glomerular retinoid-synthesizing enzymes and expression of retinoid receptors in the early repair phase of THY-GN, suggesting activation of this system in acute renal disease.

Alcohol Oxidoreductases↗
PubMed2003

Asymmetric dimethylarginine, blood pressure, and renal perfusion in elderly subjects.

BACKGROUND: Reduced availability of nitric oxide (NO) is thought to contribute to the age-associated increase of renovascular tone and blood pressure. We assessed blood concentrations of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) as well as renal hemodynamics, comparing young (n=24, 13 men, 25+/-1 years) and elderly (n=24, 13 men, 69+/-2 years) healthy subjects and elderly subjects with essential hypertension (n=24, 13 men, 70+/-2 years). METHODS AND RESULTS: Plasma ADMA concentration and renovascular resistance (RVR) were significantly higher (P<0.05) and effective renal plasma flow (ERPF) significantly lower (P<0.05) in elderly (2.77+/-0.20 micromol/L, 125+/-10 mm Hg/mL per minute, 487+/-26 mL/min per 1.73 m2) than in young healthy subjects (1.30+/-0.11, 77+/-3, 654+/-18). Both ADMA levels and RVR were higher and ERPF lower in the hypertensive elderly subjects (3.53+/-0.23, 163+/-11, 427+/-19; P<0.05 versus both groups). In contrast, plasma concentrations of the biologically inactive stereoisomer symmetric dimethylarginine, l-arginine, and homocysteine were similar in the 3 groups studied. In the logistic regression analysis only ADMA was an independent determinant of both ERPF (P<0.001; r2=0.80) and RVR (P<0.002; r2=0.86). In addition, ADMA (P<0.002) and serum glucose (P<0.036) were independently related (r2=0.67) to the level of blood pressure. CONCLUSIONS: These results are compatible with the notion that accumulation of the endogenous NO synthase inhibitor ADMA in senescent individuals is involved in the decrease of renal perfusion and increase of blood pressure.

Adult↗
PubMed2003

Myocyte loss in early left ventricular hypertrophy of experimental renovascular hypertension.

Left ventricular hypertrophy (LVH) develops very early in experimental renovascular hypertension after clipping of one renal artery and is accompanied by a remodeling of cardiac structure which has not yet been investigated in detail. It was the aim of the present study to analyze changes in cardiomyocyte number and volume in LVH after 2 weeks of renovascular hypertension. Sprague-Dawley rats were subjected to clipping of the left renal artery (2K1C) or sham operation (sham). One group of 2K1C rats received antihypertensive treatment with dihydralazine. The experiment was terminated after 2 weeks. Hearts were investigated using stereological methods, electron microscopy, immunohistology for the proliferation marker proliferating cell nuclear antigen, the pro- and anti-apoptotic proteins Bax and Bcl-2 as well as the TUNEL technique. After 2 weeks, systolic blood pressure and relative left ventricular weight were significantly higher in untreated 2K1C animals than in sham and dihydralazine-treated 2K1C rats. Volume fraction of interstitial tissue and capillary length density were not different, whereas wall thickness of intramyocardial arteries was significantly higher in untreated 2K1C (5.12+/-0.7 micro m) than in sham (3.92+/-0.6 micro m) and in dihydralazine-treated 2K1C (3.91+/-0.7 micro m) rats. Cardiomyocyte diameter and volume were significantly higher in untreated 2K1C than in sham animals. The number of cardiomyocytes per left ventricle was significantly lower in untreated 2K1C rats (5.5+/-1.6 vs 3.9+/-6.9 x10(7)). Using immunohistochemistry, no direct evidence of apoptosis was found, but a relative higher expression of the anti-apoptotic protein bcl-2 expression was seen in untreated 2K1C than in sham animals. This may reflect a protective mechanism as a consequence of earlier occurring apoptosis. These observations document that experimental renovascular hypertension induces a rapidly developing LVH characterized by marked cardiac remodeling and substantial loss of cadiomyocytes.

Animals↗
PubMed2003

Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER.

Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.

Adult↗
PubMed2003

Nephron number in patients with primary hypertension.

BACKGROUND: A diminished number of nephrons has been proposed as one of the factors contributing to the development of primary hypertension. METHODS: To test this hypothesis, we used a three-dimensional stereologic method to compare the number and volume of glomeruli in 10 middle-aged white patients (age range, 35 to 59 years) with a history of primary hypertension or left ventricular hypertrophy (or both) and renal arteriolar lesions with the number and volume in 10 normotensive subjects matched for sex, age, height, and weight. All 20 subjects had died in accidents. RESULTS: Patients with hypertension had significantly fewer glomeruli per kidney than matched normotensive controls (median, 702,379 vs. 1,429,200). Patients with hypertension also had a significantly greater glomerular volume than did the controls (median, 6.50x10(-3) mm3 vs. 2.79x10(-3) mm3; P<0.001) but very few obsolescent glomeruli. CONCLUSIONS: The data support the hypothesis that the number of nephrons is reduced in white patients with primary hypertension.

Adult↗
PubMed2003

Kidney and hypertension-causes. Update 2003.

Renal disease is closely associated with hypertension. On the one hand, kidney disease provokes hypertension. On the other hand, hypertension aggravates the progression of renal dysfunction. The pathomechanisms through which the kidney raises blood pressure have been considerably clarified in recent years. In experimental and clinical studies, it could be shown that "hypertension goes with the kidney". This suggests that some renal anomalies predispose to hypertension. Recently, it could be shown that the kidneys of individuals with so-called essential hypertension have less glomeruli than the kidneys of control individuals. In renal patients the kidney raises blood pressure through several mechanisms. First, the pressure-natriuresis relationship is shifted to the right, i. e., sodium excretion requires higher renal perfusion pressures. Second, there is inappropriate activation of the renin-angiotensin system. Third, as only recently documented in detail, renal injury raises the sympathetic tone, even when whole kidney glomerular filtration rate (GFR) is unchanged. This results from stimulating afferent signals emanating from the kidney. Fourth, there is evidence of impaired endothelial cell dependent vasodilatation even in very early stages of renal dysfunction. Fifth, the pulse pressure profile is altered as a consequence of premature and accelerated aging causing stiffening of the aorta. Knowledge of these pathomechanisms is important for selection of appropriate antihypertensive treatment.

Endothelium, Vascular↗
PubMed2003

Disorders of phosphate metabolism--pathomechanisms and management of hypophosphataemic disorders.

Hypophosphataemia does not necessarily indicate phosphate (Pi) depletion. In acute emergencies such as septicaemia, alkalosis or re-feeding, hypophosphataemia may result from redistribution of Pi from the extracellular to the intracellular space. Hypophosphataemia from true Pi depletion gives rise to skeletal (osteomalacia) and extraskeletal (myopathy, cardiomyopathy) disorders. It is practically never the result of diminished nutritional intake. The most severe syndromes of Pi depletion result from diminished tubular Pi re-absorption and renal Pi wasting. In the differential diagnosis mainly four conditions have to be considered: (i) tumour-associated osteomalacia, (ii) X-linked hypophosphataemia (XLH), (iii) autosomal dominant hypophosphataemia, and (iv) hypercalcaemic renal phosphate wasting. Recent molecular insight has put fibroblast growth factor (FGF-23) into the centre of pathophysiological considerations because of (i) overproduction (tumour-associated osteomalacia) or (ii) hypothetically, accumulation resulting from mutations causing resistance to processing or degradation (autosomal dominant hypophosphataemia) or (iii) loss-of-function of a protease (PHEX) interfering with FGF-23 breakdown (XLH). In oncogenic osteomalacia the treatment of choice is resection of the tumour. Recently, pharmacological treatment has also become possible, i.e. administration of octreotide. XLH and autosomal dominant hypophosphataemia must be managed by oral administration of phosphate and calcitriol. In patients with gastrointestinal intolerance to phosphate or with severely symptomatic bone disease, prolonged intravenous administration of Pi is necessary.

Diagnosis, Differential↗
PubMed2003

Glucose degradation products in PD fluids: do they disappear from the peritoneal cavity and enter the systemic circulation?

BACKGROUND: Glucose degradation products (GDP) are generated in peritoneal dialysis (PD) fluid during heat sterilization and storage. They are thought to adversely affect the peritoneal membrane. The fate of GDP within the peritoneal cavity has not been well characterized. METHODS: A clinical study was designed to determine (1). whether during the dwell in the peritoneal cavity GDP concentration decreases in the PD fluid as assessed by ex vivo formation of AGE; (2). whether exposure to GDP-containing PD fluids increases plasma fluorescence (as an index of plasma AGE concentration) as well as plasma carboxymethyllysine (CML) concentration; and (3). whether exposure to GDP-containing PD fluids adversely affects glycoprotein CA 125 concentration. A two-group crossover design was adopted comprising two consecutive observation periods of eight weeks each. Stable PD patients were exposed in random order either to conventional PD fluid (heat sterilized at pH 5.5) and subsequently to PD test fluid (or the 2 fluids in reverse order). The PD test fluid was sterilized using a multicompartment bag system separating highly concentrated glucose at pH 3 from the buffer solution. Conventional and test fluids differed with respect to concentrations of GDP, that is, 3-deoxyglucosone (118 vs. 12.3 micromol/L), methylglyoxal (5.3 micromol/L vs. below detection threshold), 3, 4-dideoxyglucosone-3-ene (10 micromol/L vs. below detection threshold) and acetaldehyde (226 vs. <1 micromol/L). RESULTS: The following results were obtained. First, methylglyoxal disappeared completely as early as two hours after intraperitoneal instillation of conventional PD fluid. Second, when spent conventional dialysate was recovered after a two hour and particularly an eight hour dwell and subsequently incubated ex vivo with 40 mg of human serum albumin, there was a continuous decrease of AGE-forming capacity, that is, less generation of fluorescence (AGE) and pyrraline (non-fluorescent Amadori product), and an increase of advanced oxidation protein products (AOPP) in the spent dialysate. Third, plasma fluorescence (exc. 350/em. 430 nm) as an index of circulating AGE compounds as well as plasma CML concentrations were significantly higher in the conventional PD fluid period versus low GDP PD fluid period. Fourth, CA 125 concentrations in spent dialysate were higher during the low GDP PD fluid period compared to the conventional PD fluid period. CONCLUSION: Conventional PD fluid undergoes modifications during intraperitoneal dwell with a loss of AGE forming capacity, suggesting breakdown, precipitation or resorption of GDP in vivo. This is accompanied by an increase in plasma AGE compounds.

Adult↗
PubMed2003

Hyperphosphatemia aggravates cardiac fibrosis and microvascular disease in experimental uremia.

BACKGROUND: Hyperphosphatemia is a known predictor of cardiovascular death and specifically of cardiac death in hemodialysis patients. The pathomechanisms involved have not been completely clarified. While a number of observations suggest an important role of hyperphosphatemia and positive calcium balance on atherosclerosis and calcification of the coronary conduit arteries, independent effects on postcoronary microvessels and on cardiac fibrosis have not been excluded. METHODS: Male Sprague-Dawley rats were sham operated (N = 14) or subtotally nephrectomized (SNX, N = 17) and subsequently placed on low phosphorus (0.08% w/w) and high phosphorus (1.2% w/w) diet under pair-feeding conditions. After 8 weeks, serum chemistry and inhibitory parathyroid hormone (iPTH) were measured, and the hearts were harvested using perfusion fixation. Arteriolar thickness and volume density of the interstitium (excluding vessels) were quantitated using stereologic techniques. RESULTS: In SNX animals with moderate renal failure serum phosphorus concentrations were higher than in sham-operated controls on low phosphorus diet (1.7 +/- 0.37 mmol/L) and were significantly higher in SNX + high phosphorus diet (2.33 +/- 0.23 mmol/L) compared to SNX + low phosphorus diet (1.95 +/- 0.32 mmol/L; P < 0.05). In sham-operated controls, dietary phosphorus content had no effect on cardiac morphologic indices. In contrast, in SNX + high phosphorus diet the index of interstitial cardiac fibrosis was significantly higher (3.22 +/- 0.44%) than in SNX + low phosphorus (2.75 +/- 0.46%) or in sham-operated controls (2.5 +/- 0.05% on high phosphorus and 2.4 +/- 0.89 on low phosphorus, respectively). In SNX + high phosphorus (14.0 +/- 9.0 microm), but not in SNX + low phosphorus (9.2 +/- 4.5 microm), arterial wall thickness was significantly higher compared to sham-operated controls (10.2 +/- 5.1 on high phosphorus and 9.8 +/- 5.0 micro;m on low phosphorus, respectively). The data were confirmed in an independent repeat experiment. CONCLUSION: High dietary phosphorus and hyperphosphatemia have significant effects on cardiac fibrosis and arterial wall thickening. Such abnormalities of cardiac architecture may be relevant for the increased cardiac risk in hyperphosphatemic uremic patients.

Animals↗
PubMed2003

Cardiomyocyte loss in experimental renal failure: prevention by ramipril.

BACKGROUND: The development of left ventricular hypertrophy (LVH) and of structural abnormalities of the heart is a key abnormality in renal failure that potentially contributes to the high rate of cardiac death. In renal failure, the behavior of cardiomyocyte volume and number in the development of LVH has so far not been investigated. A potential role of the (local) renin-angiotensin system (RAS) in the genesis of LVH has been suspected. It was the aim of the present study in short-term experimental renal failure (1) to characterize cardiomyocyte volume and number and (2) to study whether they are affected by the angiotensin-converting enzyme (ACE) inhibitor ramipril. METHODS: Sprague-Dawley rats (N = 8 to 10 per group) had a subtotal nephrectomy (SNX) or sham operation and followed for 8 weeks. One SNX group received the ACE inhibitor ramipril (0.5 mg/kg body weight) in the drinking fluid. After perfusion fixation, the morphology of the heart was investigated using stereologic techniques. RESULTS: Systolic blood pressure was slightly, but not significantly, higher in untreated SNX, but the left ventricular (LV) weight and LV weight/body weight ratio (2.32 +/- 0.20 mg/g) were significantly higher in SNX than in sham-operated animals (1.90 +/- 0.16 mg/g). Sarcomeric length was not significantly different between SNX and sham-operated animals. There was an increase in the number of terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL)-positive myocytes in SNX compared to sham-operated animals and a significant increase in cardiomyocyte volume (15,713 +/- 4557 microm3 vs. 10,067 +/- 2242 microm3, P < 0.01) as well as a decrease of cardiomyocyte numbers per unit myocardial volume (61.2 +/- 16.2 vs. 92.2 +/- 20.9 x 103/mm3) and per left ventricle (70.9 +/- 16.5 x 106 vs. 94.8 +/- 18.1 x 106, P < 0.05). Both abnormalities were abrogated by treatment with ramipril (6347 +/- 972.4 microm3 and 106 +/- 18.9 103/mm3 or 118 +/- 39.5 x 106, respectively), which also completely prevented the increase in LV weight/body weight ratio (1.83 +/- 0.14 mg/g). CONCLUSION: LVH in renal failure is characterized by cardiomyocyte hypertrophy, but also cardiomyocyte drop out. A role of the RAS is suggested by the beneficial effect of ramipril treatment that is not accounted for by differences in blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗