ENALAPRIL ATTENUATES THE RENAL HEMODYNAMIC-EFFECT OF ACETAZOLAMIDE INPATIENTS WITH DIABETES-MELLITUS - POSSIBLE IMPLICATIONS FOR TUBULOGLOMERULAR FEEDBACK

Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, causes a fall in renal plasma flow and glomerular filtration (GFR). It is generally be lieved that the tubuloglomerular feedback (TGF) mechanism is responsib le. This study examined whether, in patients with diabetes mellitus, t he renal hemodynamic response to ACTZ is intact and whether the angiot ensin-converting enzyme inhibitor, enalapril, which would be expected to block TGF, attenuates this response to ACTZ. Six men with insulin-d ependent diabetes mellitus lived in a clinical research center for 8 w eeks and received enalapril 5-15 mg/day from the third through sixth w eek. At 2, 6 and 8 weeks p-aminoippurate (PAH) and inulin clearances w ere performed over eleven 30-min periods. ACTZ (150 mg) was given intr avenously after 180 min, In both the pre- and postenalapril studies, P AH clearance fell after ACTZ administration (-60 +/- 15 and -66 +/- 20 ml/min/1.73 m(2), respectively, p < 0.05 for each study). In contrast , with enalapril treatment PAH clearance after ACTZ tended to rise (29 +/- 12 ml/min/1.73 m(2), p = 0.07). GFR after ACTZ fell during the pr e- and postenalapril studies (-19 +/- 3 and -13 +/- 1 ml/min/1.73 m(2) , respectively, p < 0.05 for each study) but not with enalapril treatm ent (-6 +/- 3 ml/min/1.73 m(2)). After ACTZ was administered, estimate d renal vascular resistance rose during both the pre- and postenalapri l studies (p < 0.05 and p < 0.01, respectively) and fell with enalapri l treatment (p < 0.05): These data indicate that enalapril alters the renal hemodynamic effects of ACTZ in patients with diabetes mellitus, possibly by inhibiting tubuloglomerular feedback.