title: Exogenous norepinephrine induces an enhanced microproteinuric response in microalbuminuric insulin-dependent diabetes mellitus.
abstract: Exogenous norepinephrine (NE) increases intraglomerular pressure in animal experiments, but it is unknown whether NE induces a microproteinuric response in humans. Moreover, it has not been studied whether possible microproteinuric and renal hemodynamic changes induced by NE are altered in insulin-dependent diabetes mellitus (IDDM) complicated by microalbuminuria. Therefore, the microproteinuric and renal hemodynamic responses to exogenous NE infusions were measured in eight matched normoalbuminuric IDDM patients (group D1), microalbuminuric IDDM patients (group D2), and control subjects (group C). As anticipated, mean arterial pressure (MAP)-NE dose-response curves were significantly shifted leftward in groups D1 and D2 compared with group C (P < 0.05), indicating a higher systemic NE responsiveness in IDDM. On separate days, NE or placebo was infused at individually determined NE threshold doses (T; delta MAP = 0 mmHg), 20% pressor doses (20% P; delta MAP = 4 mmHg), and pressor doses (P; delta MAP = 20 mmHg), with measurement of urinary albumin (UalbV), IgG excretion (UIgGV), GFR (by 125I-iothalamate), and effective renal plasma flow (by 131I-hippurate). At NE pressor dose, UalbV and UIgGV rose in all groups (P < 0.05 to 0.01), whereas urinary beta 2-microglobulin was unchanged. The increases in UalbV and UIgGV were more pronounced in the microalbuminuric group than in the other groups (P < 0.05). An NE dose-dependent fall in effective renal plasma flow and rise in filtration fraction were found in all groups (P < 0.05 to 0.001 for all), whereas GFR did not change significantly. The renal hemodynamic dose-response relationship was similar in the groups. In conclusion, exogenous NE acutely promotes glomerular protein leakage, and it is plausible that intraglomerular NE effects contribute to this phenomenon. The microproteinuric response is enhanced in microalbuminuric IDDM despite unaltered renal hemodynamic responsiveness, which may reflect a specific NE response or a general effect of vasopressor stimuli to promote glomerular protein leakage in patients with a preexistent defect in glomerular permselectivity.
authors.affiliation: Department of Internal Medicine, Groningen State University Hospital, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Hoogenberg
authors.forename: W J
authors.initials: WJ
authors.lastname: Sluiter
authors.forename: G
authors.initials: G
authors.lastname: Navis
authors.forename: T W
authors.initials: TW
authors.lastname: Van Haeften
authors.forename: A J
authors.initials: AJ
authors.lastname: Smit
authors.forename: W D
authors.initials: WD
authors.lastname: Reitsma
authors.forename: R P
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000503:physiopathology*; D000704:Analysis of Variance; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology* / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007074:Immunoglobulin G / Q000652:urine; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage* / Q000502:physiology*; D012016:Reference Values; D012044:Regression Analysis; D012083:Renin / Q000097:blood; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D001613:beta 2-Microglobulin / Q000187:drug effects / Q000652:urine
chemical_list: D001786:Blood Glucose; D007074:Immunoglobulin G; D007328:Insulin; D014662:Vasoconstrictor Agents; D001613:beta 2-Microglobulin; D012083:Renin; D009638:Norepinephrine