Salt-loading elevates blood pressure and aggravates insulin resistance in Wistar fatty rats: a possible role for enhanced Na+ -H+ exchanger activity.
OBJECTIVE
Increased Na+-H+ exchanger activity (NHE) has been reported as an intermediate phenotype in hypertensive subjects, particularly those with insulin resistance. To investigate whether NHE abnormality plays a role in hypertension, Wistar fatty rat (WFR) with overt obesity, hyperglycemia and marked hyperinsulinemia was examined.


METHODS
WFR and Wistar lean rats (WLR) as a control (n = 12, each) were fed either with normal (0.38%) or high sodium (4% NaCl) diet for 12 weeks and then sacrificed to examine platelets NHE activity.


RESULTS
Mean arterial pressure (MAP) was higher in WFR than in WLR (113 +/- 4 versus 96 +/- 7 mmHg, P < 0.05) under a normal chow. Vmax values of NHE activity were significantly higher in WFR than in WLR. WFR fed with a high sodium diet showed higher MAP than those with a normal chow (128 +/- 3 versus 113 +/- 4 mmHg, P < 0.05). Though Km values were not different between WFR and WLR under a normal chow, both maximal transport rate (Vmax) and half maximal transport (Km) values were significantly higher in WFR with a high salt diet than those with a control diet. Vmax showed significant correlation with MAP, whereas Km values correlated with immunoreactive insulin (IRI) levels. Significant interaction between dietary sodium intake and the strain differences was observed both on blood pressure and on IRI levels by two-way analysis of variance (ANOVA).


CONCLUSIONS
WFR presented salt-sensitive blood pressure elevation. NHE activity was enhanced in WFR in correlation with the blood pressure. These results suggest that augmented NHE activity contributes to the development of salt-sensitive blood pressure elevation in WFR.
Hayashida
T
T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Ohno
Y
Y
Otsuka
K
K
Suzawa
T
T
Shibagaki
K
K
Suzuki
H
H
Ikeda
H
H
Saruta
T
T
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D007333:Insulin Resistance; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D017923:Sodium-Hydrogen Exchangers / Q000097:blood / Q000502:physiology*; D013851:Thinness
D017923:Sodium-Hydrogen Exchangers; D012965:Sodium Chloride