Atrial natriuretic peptide and glomerular hyperfiltration during onset of spontaneous diabetes mellitus

Abstract

The mechanisms responsible for the elevation of glomerular filtration rate (GFR) in early stages of insulin-dependent diabetes mellitus (IDDM) are undefined. The objectives of this study were to define the temporal pattern of onset of glomerular hyperfiltration in the spontaneously diabetes-prone (BB/DP) rat and to evaluate the possible role of atrial 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 x g-1; n = 5) in moderately hyperglycemic BB/DP rats (blood glucose > 270 mg/dl) 14 days after the onset of IDDM compared with age-matched diabetes-resistant rats (BB/DR), which averaged 1.03 +/- 0.07 ml.min-1 x g-1 (n = 7). Circulating ANP levels in moderately hyperglycemic BB/DP rats 1, 7, and 14 days after onset of IDDM were within the normal range, averaging 100 +/- 21, 57 +/- 12, and 65 +/- 6 pg/ml, respectively, and were not significantly different (P > 0.05) from ANP levels in age-matched normoglycemic BB/DR rats. To further test the role of ANP in glomerular hyperfiltration, an ANP receptor antagonist was infused into anesthetized BB/DP rats (n = 10) 14 days after onset of IDDM, after baseline measurements of mean arterial pressure, renal hemodynamics, and renal fluid and electrolyte excretions. ANP receptor antagonism caused a significant reduction in mean arterial pressure from 120 +/- 3 to 103 +/- 2 mmHg; however, there were no significant effects of ANP receptor blockade on GFR.(ABSTRACT TRUNCATED AT 250 WORDS)