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 i nsulin resistance. To investigate whether NHE abnormality plays a role in h ypertension, Wistar fatty rat (WFR) with overt obesity, hyperglycemia and m arked 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 vers us 113 +/- 4 mmHg, P < 0.05). Though Km values were not different between W FR 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 correlati on with MAP, whereas Km values correlated with immunoreactive insulin (IRI) levels. Significant interaction between dietary sodium intake and the stra in differences was observed both on blood pressure and on IRI levels by two -way analysis of variance (ANOVA). Conclusion WFR presented salt-sensitive blood pressure elevation. NHE activ ity was enhanced in WFR in correlation with the blood pressure. These resul ts suggest that augmented NHE activity contributes to the development of sa lt-sensitive blood pressure elevation in WFR. (C) 2001 Lippincott Williams & Wilkins.