GFR normally increases during
glycine infusion. This response is absent in humans and rats with established
diabetes mellitus. In diabetic patients,
angiotensin-converting enzyme inhibition (ACEI) restores the effect of
glycine on GFR. To ascertain the glomerular hemodynamic basis for this effect of ACEI,
micropuncture studies were performed in male Wistar-Froemter rats after 5 to 6 wk of
insulin-treated
streptozotocin diabetes. The determinants of single-nephron GFR (SNGFR) were assessed in each rat before and during
glycine infusion. Studies were performed in diabetics, diabetics after 5 d of ACEI (
enalapril in the
drinking water), and weight-matched controls. Diabetic rats manifest renal
hypertrophy and glomerular hyperfiltration but not glomerular capillary
hypertension. ACEI reduced glomerular capillary pressure, increased glomerular ultrafiltration coefficient, and did not mitigate hyperfiltration. In controls,
glycine increased SNGFR by 30% due to increased nephron plasma flow. In diabetics,
glycine had no effect on any determinant of SNGFR. In ACEI-treated diabetics, the SNGFR response to
glycine was indistinguishable from nondiabetics, but the effect of
glycine was mediated by greater ultrafiltration pressure rather than by greater plasma flow. These findings demonstrate that: (1) The absent response to
glycine in established diabetes does not indicate that renal functional reserve is exhausted by hyperfiltration; and (2) ACEI restores the GFR response to
glycine in established diabetes, but this response is mediated by increased ultrafiltration pressure rather than by increased nephron plasma flow.