EXOGENOUS NOREPINEPHRINE INDUCES AN ENHANCED MICROPROTEINURIC RESPONSE IN MICROALBUMINURIC INSULIN-DEPENDENT DIABETES-MELLITUS

Exogenous norepinephrine (NE) increases intraglomerular pressure in an imal experiments, but it is unknown whether NE induces a microproteinu ric response in humans. Moreover, it has not been studied whether poss ible microproteinuric and renal hemodynamic changes induced by NE are altered in insulin-dependent diabetes mellitus (IDDM) complicated by m icroalbuminuria. Therefore, the microproteinuric and renal hemodynamic responses to exogenous NE infusions were measured in eight matched no rmoalbuminuric IDDM patients (group D1), microalbuminuric IDDM patient s (group D2), and control subjects (group C). As anticipated, mean art erial pressure (MAP)-NE dose-response curves were significantly shifte d leftward in groups D1 and D2 compared with group C (P < 0.05), indic ating a higher systemic NE responsiveness in IDDM. On separate days, N E or placebo was infused at individually determined NE threshold doses (T; Delta MAP = 0 mmHg), 20% presser doses (20% P; Delta MAP = 4 mmHg ), and presser doses (P; Delta MAP = 20 mmHg), with measurement of uri nary albumin (U-alb V), IgG excretion (UIgGV), GFR (by I-125-iothalama te), and effective renal plasma flow (by I-131-hippurate). At NE press er dose, UalbV and UIgGV rose in all groups (P < 0.05 to 0.01), wherea s urinary beta(2)-microglobulin was unchanged. The increases in UalbV and UIgGV were more pronounced in the microalbuminuric group than in t he other groups (P < 0.05). An NE dose-dependent fall in effective ren al plasma flow and rise in filtration fraction were found in all group s (P < 0.05 to 0.001 for all), whereas GFR did not change significantl y. The renal hemodynamic dose-response relationship was similar in the groups. In conclusion, exogenous NE acutely promotes glomerular prote in leakage, and it is plausible that intraglomerular NE effects contri bute to this phenomenon. The microproteinuric response is enhanced in microalbuminuric IDDM despite unaltered renal hemodynamic responsivene ss, which may reflect a specific NE response or a general effect of va sopressor stimuli to promote glomerular protein leakage in patients wi th a preexistent defect in glomerular permselectivity.