ATRIAL-NATRIURETIC-PEPTIDE AND GLOMERULAR HYPERFILTRATION DURING ONSET OF SPONTANEOUS DIABETES-MELLITUS

The mechanisms responsible for the elevation of glomerular filtration rate (GFR) in early stages of insulin-dependent diabetes mellitus (IDD M) are undefined. The objectives of this study were to define the temp oral pattern of onset of glomerular hyperfiltration in the spontaneous ly diabetes-prone (BB/DP) rat and to evaluate the possible role of atr ial natriuretic peptide (ANP) as the primary mediator of the observed alterations in renal hemodynamics. GFR was significantly higher (1.38 +/- 0.07 ml.min(-1).g(-1); n = 5) in moderately hyperglycemic BB/DP ra ts (blood glucose > 270 mg/dl) 14 days after the onset of IDDM compare d with age-matched diabetes-resistant rats (BB/DR), which averaged 1.0 3 +/- 0.07 ml.min(-1).g(-1) (n. = 7). Circulating ANP levels in modera tely hyperglycemic BB/DP rats 1, 7, and 14 days after onset of IDDM we re within the normal range, averaging 100 +/- 21, 57 +/- 12, and 65 +/ - 6 pg/ml, respectively, and were not significantly different (P > 0.0 5) from ANP levels in age-matched normoglycemic BB/DR rats. To further test the role of ANP in glomerular hyperfiltration, an ANP receptor a ntagonist was infused into anesthetized BB/DP rats (n = 10) 14 days af ter onset of IDDM, after baseline measurements of mean arterial pressu re, renal hemodynamics, and renal fluid and electrolyte excretions. AN P receptor antagonism caused a significant reduction in mean arterial pressure from 120 +/- 3 to 103 +/- 2 mmHg; however, there were no sign ificant effects of ANP receptor blockade on GFR. These results indicat e that 1) glomerular hyperfiltration occurs within the first 2 wk afte r onset of IDDM in the moderately hyperglycemic BB/DP rat and 2) ANP i s not the primary mediator of glomerular hyperfiltration during the on set of diabetes in this animal model of spontaneous IDDM.