Effect of high NaCl diet on spontaneous hypertension in a genetic rat model with reduced nephron number.
OBJECTIVE
An inherited reduction in nephron number has been implicated in the development of salt-sensitive hypertension and end stage renal disease. The Munich Wistar Frömter (MWF) rat represents a genetic model with a 30-50% reduction of nephrons compared with normal rats. MWF rats develop spontaneous hypertension and increased urinary albumin excretion (UAE). We addressed the question whether the inherited defect in this model leads to salt-sensitive hypertension.


METHODS
At the age of 6 weeks, we started male and female MWF/Fub rats and salt-resistant Lewis (Lew) reference rats on either a normal NaCl (0.2%) or a high NaCl (8%) diet (n = 8, each group). Systolic blood pressure (SBP) and UAE were measured at 14 weeks.


RESULTS
Under a normal diet, MWF/Fub rats demonstrated significantly elevated SBP compared to Lew rats both in male (165 +/- 2 versus 133 +/- 3 mmHg, P < 0.0001) and female (156 +/- 3 versus 134 +/- 3 mmHg, P < 0.0001) rats. After high NaCl treatment, SBP was significantly higher in both male and female MWF/Fub rats (+55 mmHg and +36 mmHg, P < 0.0001, respectively) compared with MWF/ Fub under a normal diet UAE was also significantly higher in male and female MWF/Fub rats after high NaCl excess (P < 0.0005, respectively). In contrast, both SBP and UAE remained unchanged in response to high NaCl in Lew rats.


CONCLUSIONS
Our findings demonstrate that both the hypertension and UAE are sensitive to high NaCl loading in female and male MWF/Fub rats. Thus, an inborn nephron deficit may lead to salt-sensitive hypertension and renal dysfunction.
Kreutz
R
R
Department of Clinical Pharmacology and Toxicology, Benjamin Franklin Hospital, Freie Universität Berlin, Germany. kreutz@medizin.fu-berlin.de
Kovacevic
L
L
Schulz
A
A
Rothermund
L
L
Ketteler
M
M
Paul
M
M
D000419:Albuminuria / Q000209:etiology; D000818:Animals; D001794:Blood Pressure; D004039:Diet, Sodium-Restricted; D005260:Female; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology / Q000652:urine; D008297:Male; D009399:Nephrons / Q000002:abnormalities*; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains / Q000235:genetics; D012016:Reference Values