title: Impaired endothelial function in patients with nephrotic range proteinuria.
abstract: Proteinuria is associated with increased cardiovascular morbidity and mortality. Release of nitric oxide by the endothelium has been advanced as an important defense mechanism against vessel-wall damage. In the present study we therefore tested the hypothesis that proteinuria is associated with a defect in nitric oxide-dependent vasodilation, by using venous occlusion plethysmography of the forearm in nine patients with nephrotic range proteinuria (> 3.5 g/24 hr) and normal renal function (creatinine 83.1 +/- 8.7 mumol/liter), eight patients with active glomerulonephritis but normal renal function (creatinine 81.2 +/- 5.4 mumol/liter) and low range proteinuria (< 1.0 g/24 hr), and ten healthy volunteers. We infused L-NMMA (2 mg/min) to inhibit basal nitric oxide production, serotonin (0.1, 0.3 and 1.0 ng/kg/min) as an endothelium-dependent vasodilator, and nitroprusside (1, 10, 30 and 100 ng/kg/min) as an endothelium-independent vasodilator into the brachial artery. Administration of L-NMMA decreased basal forearm vascular resistance (FVR) by 30 +/- 4% in the nephrotic subjects, 38 +/- 4% in the non-nephrotic patients and by 37 +/- 2% in the healthy controls (P = 0.15). Upon the highest dose of serotonin FVR decreased in nephrotic subjects by 40 +/- 5%, which was less than in non-nephrotic patients (56 +/- 3%; P < 0.05) or in healthy controls (55 +/- 3%; P < 0.05). The maximal decrease in FVR upon nitroprusside infusion was not different between the groups (respectively 84 +/- 2, 84 +/- 3 and 84 +/- 2%). The impaired serotonin-induced vasodilation could be attributed to a defect in nitric oxide production, since L-NMMA almost completely prevented serotonergic vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Nephrology and Hypertension, Academic Hospital Utrecht, The Netherlands.
authors.forename: E S
authors.initials: ES
authors.lastname: Stroes
authors.forename: J A
authors.initials: JA
authors.lastname: Joles
authors.forename: P C
authors.initials: PC
authors.lastname: Chang
authors.forename: H A
authors.initials: HA
authors.lastname: Koomans
authors.forename: T J
authors.initials: TJ
authors.lastname: Rabelink
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D005921:Glomerulonephritis / Q000503:physiopathology; D006801:Humans; D008297:Male; D009401:Nephrosis / Q000503:physiopathology / Q000652:urine*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010991:Plethysmography; D011507:Proteinuria / Q000503:physiopathology*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D019323:omega-N-Methylarginine
chemical_list: D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D012701:Serotonin; D001120:Arginine