Submitted on September 26, 2003
Accepted on December 1, 2003
EFFECTS OF INSULIN ON RENAL INTERSTITIAL HYDROSTATIC PRESSURE AND NATRIURETIC RESPONSE TO VOLUME EXPANSION IN DIABETIC RATS
Daiyi Tang1, Tianzheng Yu1, and Ali A Khraibi1*
1 Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA, USA
* To whom correspondence should be addressed. E-mail: khraibaa{at}evms.edu.
Diabetes mellitus (DM) is characterized by alterations in fluid balance and blood volume homeostasis. Renal interstitial hydrostatic pressure (RIHP) has been shown to play a critical role in mediating sodium and water excretion under various conditions. The objective of this study was to determine the effects of immediate and delayed initiation of insulin treatment on the restoration of the relationship between RIHP, natriuretic, and diuretic responses to acute saline volume expansion (VE) in diabetic rats. Diabetes was induced by an intraperitoneal (i.p.) injection of streptozotocin (STZ; 65 mg/kg body wt). Four groups of female Sprague Dawley (SD) rats were studied: normal control group (C); untreated diabetic group (D); immediate insulin treated diabetic group (DI; treatment with insulin for two weeks was initiated immediately when diabetes was confirmed which was two days after STZ injection); delayed insulin treated diabetic group (DDI; treatment with insulin for two weeks was initiated two weeks after STZ injection). RIHP, and sodium and water excretions were measured before and during VE (5% body wt/30 min) in the four groups of anesthetized rats. VE significantly increased RIHP, fractional excretion of sodium (FENa), and urine flow rate (V) in all groups of rats. Basal RIHP, RIHP response to VE (
RIHP), and FENa and V responses to VE (FENa and V) were significantly lower in the D group as compared with the C group of rats. RIHP was significantly higher in both DI and DDI groups as compared with D group, but was similar to that of the C group of rats. While in the DI group, FENa response to VE was restored, FENa was significantly increased in DDI as compared with D group, but it remained lower than that of the C group. In conclusion insulin treatment initiated immediately after the onset of diabetes restores basal RIHP, and RIHP, natriuretic, and diuretic responses to VE; however, delayed insulin treatment restores the basal RIHP and RIHP response to VE, but does not fully restore the natriuretic response to VE.
