Impaired endothelial function in patients with nephrotic range proteinuria

Kidney Int. 1995 Aug;48(2):544-50. doi: 10.1038/ki.1995.325.

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)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Endothelium, Vascular / physiopathology*
  • Female
  • Forearm / blood supply
  • Glomerulonephritis / physiopathology
  • Humans
  • Male
  • Nephrosis / physiopathology
  • Nephrosis / urine*
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism
  • Nitroprusside / pharmacology
  • Plethysmography
  • Proteinuria / physiopathology*
  • Reference Values
  • Regional Blood Flow / drug effects
  • Serotonin / pharmacology
  • omega-N-Methylarginine

Substances

  • Nitroprusside
  • omega-N-Methylarginine
  • Nitric Oxide
  • Serotonin
  • Arginine