Effects of salt loading on glucose tolerance, blood pressure, and albuminuria in rats with non-insulin-dependent diabetes mellitus

Abstract

We studied the effects of salt loading on glucose tolerance, blood pressure, and albuminuria in rats with mild non-insulin-dependent diabetes mellitus (NIDDM). Two-day-old male Wistar Kyoto (WKY) rats were injected intraperitoneally (IP) with either 75.0 mg/kg streptozotocin (STZ) or vehicle as control. Salt loading was performed as 1% NaCl of drinking solution from 4 weeks until 12 weeks of age (estimated sodium intake: control, 3.14 ± 0.28 mEq/d in tap-water group, 11.9 ± 0.95 mEq/d in salt-loaded group; NIDDM, 2.93 ± 0.16 mEq/d in tap-water group, 12.0 ± 2.59 mEq/d in salt-loaded group). Oral glucose tolerance, glycosylated hemoglobin (GHb), and pancreatic insulin content at 12 weeks did not differ between the salt-loaded group and tap-water group in both NIDDM and control rats. Urinary sodium excretion was increased in salt-loaded groups of control and NIDDM rats, but systolic blood pressure did not differ among the groups (control, 151 ± 6 mm Hg in tap-water group, 150 ± 3 mm Hg in salt-loaded group; NIDDM, 152 ± 3 mm Hg in tap-water group, 157 ± 2 mm Hg in salt-loaded group). Urinary albumin excretion was significantly increased in salt-loaded groups (1,790 ± 272 μg/d in control, 1,617 ± 174 μg/d in NIDDM rats) compared with tap-water groups (691 ± 75 μg/d in control, P < .05; 616 ± 69 μg/d in NIDDM rats, P < .001), irrespective of STZ injection, but endogenous creatinine clearance was not different among the groups. Furthermore, renal growth was more greatly increased in salt-loaded groups. The present study demonstrated that high salt intake led to an increase in albuminuria and kidney weight without elevating the glycemic and blood pressure levels or without inducing hyperfiltration in both control and NIDDM rats. These results suggest that salt loading, per se, may be harmful to kidneys.