Urinary excretion of vasoactive substances in chronic renal failure.
To investigate the pathophysiological role of vasoactive substances in the progression of chronic renal disease, we measured the 24-hour urinary excretion of prostaglandin 6-keto F1alpha, thromboxane B2, NOx, cGMP and ET-1 in 26 patients with chronic renal failure under conservative treatment and in 40 control subjects. Urinary 6-keto PgF1alpha, TxB2 and cyclic GMP were evaluated by RIA, and ET-1 was assayed by EIA. NOx were evaluated using a colorimetric assay as nitrate/nitrite. Urinary excretion of prostaglandin 6-keto F1alpha averaged 18.1 +/- 20.9 ng/g Ucreat in patients vs. 240.9 +/- 257.3 in controls (p < 0.0001), thromboxane B2 422 +/- 374 ng/g Ucreat in patients vs. 967 +/- 589 in controls (p < 2x 10(-5)), NOx 7.07 +/- 5.54 mg/g Ucreat in patients vs. 9.79 +/- 3.77 in controls (p < 0.01), cGMP 310 +/- 200 pg/g Ucreat in patients vs. 488 +/- 241 in controls (p < 0.001). In contrast, ET-1 urinary excretion was almost doubled in patients (13.45 +/- 5.84 ng/g of Ucreat) in comparison with controls (6.84 +/- 2.81 p < 1x10(-5)). While in control subjects significant correlations between urinary excretions of prostaglandin 6-keto F1alpha and thromboxane B2 (r = 0.69, p < 0.001) or NOx and ET-1 (r = 0.54, p < 0.001) were present, in patients only the relationship between urinary excretions of prostaglandin 6-keto F1alpha and thromboxane B2 (r = 0.53, p < 0.01) was retained. Our data suggest that in the normal kidney a balance between prostaglandin I2 and thromboxane A2, or nitric oxide and endothelin-1 is present, which contributes to hemodynamic regulation and protects this organ from ischemic damage. This balance is abolished in CRF, where a large increment of vasopressor agent endothelin is present, which, joined to a prevalent decrease of prostaglandin I2 synthesis, could contribute to the ischemic and fibrogenetic damage of the kidney, leading to progression of renal disease.
Cantaro
S
S
Division of Nephrology,  University of Padova, Italy. helios@ux1.unipd.it
Milan Manani
S
S
Marcon
R
R
Bonfante
L
L
Masiero
M
M
D'Angelo
A
A
Calò
L
L
D015121:6-Ketoprostaglandin F1 alpha / Q000502:physiology / Q000652:urine; D000328:Adult; D000368:Aged; D003404:Creatinine / Q000652:urine; D006152:Cyclic GMP / Q000502:physiology / Q000652:urine; D019332:Endothelin-1 / Q000502:physiology / Q000652:urine; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000502:physiology / Q000652:urine; D009569:Nitric Oxide / Q000502:physiology / Q000652:urine; D009573:Nitrites / Q000494:pharmacology / Q000652:urine; D013929:Thromboxane B2 / Q000502:physiology / Q000652:urine; D014666:Vasomotor System / Q000502:physiology*
D019332:Endothelin-1; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003404:Creatinine; D006152:Cyclic GMP