Glomerulosclerosis and progression: Effect of subantihypertensive doses of α and βblockers

Amann, Kerstin; Koch, Andreas; Hofstetter, Jürgen; Gross, Marie–Luise; Haas, Christian; Orth, Stephan R.; Ehmke, Heimo; Rump, Lars Christian; Ritz, Eberhard

doi:10.1046/j.1523-1755.2001.00936.x

Cited by 98 publications

(97 citation statements)

References 40 publications

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“…It is known that the sympathetic nervous system is overactive in patients with chronic renal damage. 25 Amman et al 26 reported that alpha-and beta-blockers, and their combination, had a beneficial effect on renal morphology and albuminuria in a rat model of renal ablation. Moreover, it has been reported that OHT might be associated with overactivity of the sympathetic nervous system.…”

Section: Discussionmentioning

confidence: 99%

Orthostatic hypertension: home blood pressure monitoring for detection and assessment of treatment with doxazosin

et al. 2011

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To determine the role of home blood pressure (BP) monitoring for a reproducible assessment of orthostatic hypertension (OHT) and the effectiveness of hypertension control by doxazosin. In this study, 605 medicated hypertensive outpatients were enrolled. Home BP in the sitting and standing positions was monitored in all patients in the morning and evening for 6 months. According to an open-label multicenter trial design, the patients were randomly allocated to either an intervention group that took doxazosin (1-4 mg) at bedtime or to a control group that did not receive any add-on medication. The patients were divided into deciles of orthostatic BP change as evaluated by home BP monitoring at baseline. Those in the top decile, in the lowest decile and in deciles two through eight were then assigned to the OHT group, the orthostatic hypotension group and the orthostatic normotension group, respectively.Orthostatic BP in the OHYPO group did not change, whereas that of the OHT group was markedly reduced by doxazosin (Po0.01). In the control group, classification into orthostatic BP categories using home BP monitoring was more reproducible (j coefficient: 0.42-0.50) than when using clinical BP (j coefficient: 0.13-0.24). In all groups, a reduction in the urinary albumin/creatinine ratio was significantly associated with a reduction in orthostatic BP doxazosin (Po0.001).The identification of OHT based on home BP monitoring was highly reproducible. The administration of doxazosin might control OHT and consequently prevent target organ damage.

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Section: Discussionmentioning

confidence: 99%

Orthostatic hypertension: home blood pressure monitoring for detection and assessment of treatment with doxazosin

et al. 2011

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“…17,18 Analysis of glomerular capillarization and cellularity on semithin sections On five semithin sections per animal, glomerular capillarization and cellularity were analyzed using the point counting method and a 100-point eyepiece (Integrationsplatte II; Zeiss Co.) at a magnification of Â 1000 (oil immersion) as described previously. 19 Briefly, the length density (L v …”

Section: Glomerular Geometrymentioning

confidence: 99%

“…18,19 Briefly, total RNA (1 mg) was dissolved in 20 ml of a reaction mixture containing 4 mM dATP, dCTP, dTTP and dGTP; 10 U RNAsin (Life Technologies BLR, Grand island, NY, USA); 100 pmol random hexamers (Boehringer Mannheim GmbH, Mannheim, Germany); PCR buffer (final concentrations: 1.6 mM (NH 4 ) 2 SO 4 , 2.0 mM Tris-HCl (pH 8.4), 1.5 mM MgCl 2 ); and 100 U Superscript reverse transcriptase (Life Technologies BLR). After incubation at 421C for 45 min, the enzyme was denatured for 5 min at 941C.…”

Section: Immunohistochemical Investigationsmentioning

confidence: 99%

Renoprotective effect of a dopamine D3 receptor antagonist in experimental type II diabetes

Gross

Koch

Mühlbauer

et al. 2006

Laboratory Investigation

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Diabetic nephropathy is the leading cause of end-stage renal disease. Dopamine receptors are involved in the regulation of renal hemodynamics and may play a role in diabetes-induced hyperfiltration. To test this hypothesis, we investigated the renal effect of a dopamine D3 receptor antagonist (D3-RA) in hypertensive type II diabetic SHR/N-cp rats. Lean and obese SHR/N-cp rats were randomly assigned to D3-RA, angiotensinconverting enzyme inhibitor (ACE-i), or D3-RA þ ACE-i treatment or control conditions. Treated animals were given the D3-RA A-437203 (10 mg/kg/body weight (BW)/day) or the ACE-i trandolapril (0.3 mg/kg BW/day) or a combination of both. At 6 months following perfusion, fixed kidneys were analyzed by morphological and stereological methods. Indices of renal damage (glomerulosclerosis, glomerulosclerosis damage index (GSI), tubulointerstitial and vascular damage), glomerular geometry and functional variables such as urinary albumin excretion, glomerular filtration rate, blood pressure, blood chemistry and BW were determined. The GSI (score 0-4) was significantly higher (Po0.05) in untreated diabetic animals (1.6270.3) compared to nondiabetic controls (0.470.2) and the treatment groups (D3-RA: 0.3170.12; ACE-i: 0.2970.1; combination treatment: 0.1270.01). Urinary albumin excretion (mg/24 h) was higher in untreated diabetic controls (102719) compared to nondiabetic controls (31712) and the treatment groups (D3-RA: 44715; ACE-i: 41713; combination treatment: 1578). Mean glomerular volume was higher in untreated diabetic animals compared to nondiabetic controls and to the treatment groups. Desmin expression, a marker of podocyte damage, was elevated in untreated diabetic controls and diminished in all treatment groups. These data suggest that in a model of type II diabetes, the dopamine D3-RA had a beneficial effect on renal morphology and albuminuria, which was comparable in magnitude to that of ACE-i treatment.

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“…The volume density of the various cell types (V VCell ) and the cell density per volume (N VCell ) were determined according to the equation N VCell ϭ k/␤ ϫ N ACell 1.5 /V VCell 0.5 , with ␤ ϭ 1.5 for podocytes, ␤ ϭ 1.4 for mesangial and endothelial cells, and k ϭ 1 (19) …”

Section: Glomerular Capillarization Cellularity and Cell Proliferationmentioning

confidence: 99%

“…The vessel area (A vessel ) and lumen area (A lumen ) were determined with the equations A vessel ϭ ϫ (D outer /2) 2 and A lumen ϭ ϫ (D inner /2) 2 , respectively (D outer , distance from one outer site of the vessel to the opposite site; D inner , distance from one inner site of the vessel to the opposite site; D max , D outer Ϫ D inner at the largest vessel diameter; D min , D outer Ϫ D inner at the smallest vessel diameter). The lumen of the vessel was calculated as the difference of the two (19).…”

Section: Quantitative Analysis Of the Renal Vasculaturementioning

confidence: 99%

Glomerular and Renal Vascular Structural Changes in α8 Integrin-Deficient Mice

Haas¹,

Amann²,

Schittny³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Integrins are matrix receptors that regulate cell-matrix interactions during development and in adult tissue. In the adult kidney, the ␣8 chain is specifically expressed in glomerular mesangial cells and vascular smooth muscle cells. ␣8-deficient (␣8Ϫ/Ϫ) mice demonstrate reductions in renal mass, which can range from complete renal agenesis to the development of kidneys that are only slightly smaller than wild-type kidneys. No histologic abnormalities of these kidneys have been described. However, considering the prominent expression of ␣8 in glomeruli and renal vessels, it seemed unlikely that the kidneys of ␣8Ϫ/Ϫ mice would be completely normal. Therefore, the renal phenotype of adult ␣8Ϫ/Ϫ mice was investigated, for assessment of more subtle morphologic alterations in kidney tissue. ␣8Ϫ/Ϫ mice displayed a significant reduction in nephron number and an increase in glomerular volume, compared with wild-type control animals. Albuminuria was not different in wild-type and ␣8Ϫ/Ϫ mice. Quantitative morphologic analyses revealed that the glomeruli of ␣8Ϫ/Ϫ mice were hypercellular, with an increased number of mesangial cells, compared with wild-type mice. Mesangial matrix deposition (as demonstrated for collagen IV and the ␣8 ligand fibronectin) was expanded in ␣8Ϫ/Ϫ mice, compared with wild-type mice. Collagens I and III, which are not normally present in glomeruli, were detected in the glomeruli of ␣8Ϫ/Ϫ mice. Staining for other glomerular integrins demonstrated an increased abundance of the collagen receptor ␣2 integrin in ␣8Ϫ/Ϫ mice. The glomerular capillary length density was significantly greater in ␣8Ϫ/Ϫ mice than in wild-type mice. Cortical arterial vessel walls were not altered in ␣8Ϫ/Ϫ mice, but the capillaries of the peritubular network were widened. Despite the strong mesangial and vascular expression of ␣8, glomerular and renal vascular alterations in ␣8Ϫ/Ϫ mice were relatively mild. Only aged ␣8Ϫ/Ϫ mice demonstrated increased glomerular capillary widening, compared with control animals. The results suggest that the lack of ␣8 can be largely compensated for, at least in younger ␣8Ϫ/Ϫ mice. It is not yet clear whether the occurrence of collagens that are not normally present in glomeruli and the increased abundance of the collagen receptor ␣2 contribute to maintaining the glomerular structure in ␣8Ϫ/Ϫ mice. The compensatory mechanisms involved will be the subject of future research.Integrins are heterodimeric transmembrane glycoproteins, each consisting of two noncovalently linked chains, the ␣ and ␤ subunits. Eighteen ␣ and eight ␤ chains have been identified; they combine to form 24 integrin receptor types (1). Cellmatrix interactions mediated mainly by integrins of the ␤1 family play important roles in embryogenesis and maintenance of the normal structure and function of organs, including the kidney (1). Furthermore, many human and experimental renal diseases are associated with altered expression of integrins (2), pointing to an important role for integrins in the development and/or progress...

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Glomerulosclerosis and progression: Effect of subantihypertensive doses of α and βblockers

Cited by 98 publications

References 40 publications

Orthostatic hypertension: home blood pressure monitoring for detection and assessment of treatment with doxazosin

Orthostatic hypertension: home blood pressure monitoring for detection and assessment of treatment with doxazosin

Renoprotective effect of a dopamine D3 receptor antagonist in experimental type II diabetes

Glomerular and Renal Vascular Structural Changes in α8 Integrin-Deficient Mice

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