ISOSORBIDE-5 MONONITRATE ADMINISTRATION INCREASES NITRIC-OXIDE BLOOD-LEVELS AND REDUCES PROTEINURIA IN IGA GLOMERULONEPHRITIS PATIENTS WITHABNORMAL URINARY ENDOTHELIN CYCLIC-GMP RATIO

An endothelin urinary hyperexcretion, which is not counterbalanced by an adequate increase in cGMP biosynthesis, was previously detected in some patients with IgA Nephropathy (IgAN). Since this imbalance might potentiate local ET(1)-mediated hemodynamics effects, 9 IgAN patients with an increased (20.1) urinary ET(1)/cGMP ratio (group 1) and 5 IgAN patients with comparable renal function and reduced ET(1)/cGMP ratio (group 2) were given standard doses of isosorbide 5 mononitrate (as a nitric oxide source). Blood nitric oxide (NO) levels, as detected by e lectron paramagnetic resonance, significantly increased after isosorbi de administration (p < 0.01) and decreased after drug discontinuation in both groups. Nitric oxide levels were significantly related with th ose of the effective renal plasma flow (p < 0.02), but not with the gl omerular filtration rate. Proteinuria levels significantly decreased a fter drug administration (p < 0.009) in group 1 and returned to baseli ne levels thereafter, except two cases showing persisting low levels. Values of filtration fraction in the same group decreased after iso5M administration (p < 0.02 compared to basal levels). These results may possibly be related to the counterbalancing effects of nitric oxide on endothelin-mediated mesangial contraction.