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Impact of Nephron Number Dosing on Cardiorenal Damage and Effects of ACE Inhibition.
MedLine Citation:
PMID:  20864942     Owner:  NLM     Status:  In-Data-Review    
BackgroundLow nephron number is a recently identified cause of arterial hypertension. We set out to test the effect of nephron number dosing on blood pressure and cardiorenal damage including left ventricular (LV) remodeling and function. Because exact determination of nephron number in vivo is currently not possible, we combined the Munich Wistar Frömter (MWF) genetic rat model of inborn nephron deficit with the 5/6 renal ablation model (Nx).MethodsTo obtain distinct levels of nephron number dose (NND), rats underwent either sham-operation (Wistar-Sham NND 1.0, and MWF-Sham NND 0.6, n = 15, respectively) or 5/6 renal ablation (Nx, Wistar-Nx NND 0.17, and MWF-Nx NND 0.1, n = 20, respectively). Two additional groups were treated orally for 4 weeks with 1 mg/kg/day ramipril (Wistar-Nx-ACEI and MWF-Nx-ACEI, n = 15, respectively).ResultsSystolic blood pressure (SBP), LV hypertrophy, mRNA expression of atrial natriuretic factor, LV contractility, and relaxation were exponentially correlated with NND (P < 0.0001, respectively). Creatinine clearance (Cl(Cr)) decreased, albuminuria, renal interstitial fibrosis, tubulointerstitial damage, and glomerulosclerosis index increased with lowering NND in both Wistar-Nx (NND 0.17) and MWF-Nx (NND 0.1) animals. LV perivascular and interstitial fibrosis and sarcoplasmic reticular (SR) Ca(2+) cycling were not directly related to NND. Angiotensin-converting enzyme (ACE) inhibition with ramipril demonstrated strong cardio- and renoprotective effects even in the setting of very low NND of 0.1 in MWF-Nx animals.ConclusionsThese data demonstrate that reduced nephron number is a significant, independent determinant of blood pressure, cardiorenal damage, and LV dysfunction in a direct dose-dependent way.American Journal of Hypertension (2011). doi:10.1038/ajh.2010.206.
Lars Rothermund; Marcus Lorenz; Anne Schnieber; Jan Eberson; Iris Bauhaus; Marcel Bernhard Haug; Angela Schulz; Frieder Keller; Roland Vetter; Reinhold Kreutz
Publication Detail:
Type:  Journal Article     Date:  2010-09-23
Journal Detail:
Title:  American journal of hypertension     Volume:  24     ISSN:  1879-1905     ISO Abbreviation:  Am. J. Hypertens.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8803676     Medline TA:  Am J Hypertens     Country:  United States    
Other Details:
Languages:  eng     Pagination:  474-81     Citation Subset:  IM    
1] Institut für Klinische Pharmakologie und Toxikologie, Campus Benjamin Franklin und Campus Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany [2] KfH Nierenzentrum Ulm, Ulm, Germany.
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