Impaired endothelial function in patients with nephrotic range proteinuria.
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)
Stroes
E S
ES
Department of Nephrology and Hypertension, Academic Hospital Utrecht, The Netherlands.
Joles
J A
JA
Chang
P C
PC
Koomans
H A
HA
Rabelink
T J
TJ
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
D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D012701:Serotonin; D001120:Arginine