Renal functional reserve in treated and untreated hypertensive rats

Abstract

Renal functional reserve (renal response to protein loading, RFR) has been suggested as a method to verify the presence of hyperfiltration. This study was designed to evaluate the role of RFR as an indicator of increased glomerular capillary hydrostatic pressure in short-term treated and untreated rats with two-kidney, one-clip Goldblatt hypertension. One month after placing a silver clip, micropuncture studies were performed on the unclipped kidney. Normal rats and three groups of clipped rats [untreated group (HYP), a group treated with captopril (CEI) and a group treated with verapamil (VER) 5 days before the micropuncture studies] were studied. Glomerular hemodynamics and proximal tubular reabsorption were measured in control period and during intravenous administration of glycine (G). In normal rats, G produced afferent and efferent dilation, increases in single nephron plasma flow (SNPF) and single nephron glomerular filtration rate (SNGFR) of 24%. Systemic hypertension in HYP rats was associated with increases in transcapillary pressure gradient (ΔP) and SNGFR. In this hyperfiltration state, infusion of G did not modify SNGFR of SNPF defining loss of RFR. The antihypertensive treatment was equally effective in normalizing MAP and ΔP in CEI and VER, but only CEI rats responded to G with a 20% increase in SNGFR due to an increase in ΔP. The most striking findings were that loss of RFR in both HYP and VER rats was associated with a significant decrease in absolute and proximal fractional reabsorption. We conclude that: 1) loss of RFR is not always associated with the presence of glomerular hypertension; and 2) decreases in proximal tubular reabsorption strongly correlate with loss of RFR, suggesting an important role for tubular function in the glomerular hemodynamic response to intravenous amino acid infusion.