The present work demonstrated that systemic treatment with an NO donor before reperfusion improved renal function and diminished inflammatory responses in a kidney subjected to an I-R process.

The effects of reactive oxygen species (ROS) on cultured rat mesangial cells were studied by measuring planar cell surface area (PCSA) after incubation with xanthine plus xanthine oxidase (XXO), in the presence of superoxide dismutase (SOD; 5 micrograms/ml) or catalase (CAT; 20 micrograms/ml), or after incubation with H2O2. Myosin light chain (MLC) phosphorylation was assessed in cells prelabeled with o-[32P]phosphoric acid and incubated with H2O2, after protein separation with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A possible intermediate role for platelet-activating factor (PAF) was analyzed by preincubation of the cells with a PAF antagonist BN 52021 (BN, 5 x 10(-5) M) and by measuring PAF-specific [3H]acetate incorporation and immunoassayable PAF. XXO significantly decreased PCSA (14%), an effect abolished by CAT but not by SOD. H2O2 induced a similar effect, in a dose-dependent and time-dependent manner. MLC phosphorylation increased by 81 +/- 15% after H2O2 incubation, and this effect was blocked by BN. BN also completely blocked the effect of H2O2 on PCSA. PAF-specific [3H]acetate incorporation increased in the presence of H2O2 (from 6,886 +/- 2,030 to 58,703 +/- 16,063 counts.min-1.mg-1) as well as the immunoassayable PAF production by cells (from 0.90 +/- 0.19 to 6.71 +/- 2.27 ng/mg). These results suggest that ROS, particularly H2O2, could modulate the surface area of mesangial cells, modifying the ultrafiltration coefficient, thus explaining the decrease in glomerular filtration rate in those pathological situations characterized by an increased ROS synthesis. PAF could be involved in the genesis of these effects.

(PRL) secretion was investigated in 12 undialyzed patients with chronic renal failure (CRF), 30 hemodialyzed patients (HD), 19 renal transplant (RT) recipients and 17 controls. Basal PRL levels in CRF and HD patients were higher than in controls and RT subjects. Plasma PRL values were higher in CRF than in HD patients. In the HD group, plasma PRL concentrations were significantly higher in men with reduced sexual potency than in those in which it was normal. After TRH stimulation in CRF and HD the PRL response was considerably less and the time of peak delayed with respect to the controls. In RT subjects PRL did not return towards baseline after 120 min. After bromocriptine, plasma PRL suppression in CFR and HD patients was lower than in controls and RT subjects. These findings suggest that some factor which accumulates in uremia, is only partially removed by hemodialysis, and might be responsible for the hyperprolactinemia and might also interfere with the binding of TRH and bromocriptine to their respective pituitary receptors. Although a pituitary defect seems to be prevalent, a concomitant hypothalamic disorder cannot be excluded. Hyperprolactinemia seems to play a role in the sexual disturbances showed by some HD men. Whatever the alterations responsible for the impaired PRL regulation in uremia are, they are reversed by successful renal transplant.

SUMMARY1. Endothelin (ET) has been shown to reduce glomerular filtration rate (GFR) and renal blood flow (RBF) and may therefore be a possible mediator of the reduction of GFR and RBF observed in post-ischaemic acute renal failure.2. We infused a specific ET antibody, i.v., for 1 h before and 1 h after a 60 min period of renal ischaemia by clamping the renal artery, and observed the changes in renal function (acute clearance and long-term metabolic cage studies) compared with rats infused with non-immune rabbit serum.3. In acute and long-term studies, better renal function, as judged by GFR and RBF was observed in rats treated with the ET antibody. Furthermore, ischaemic rats showed higher levels of plasma immunoreactive ET (7-02 + 1-17 pg ET (ml plasma)-'; mean+ S.E.M.) than normal rats where it was undetected.4. We previously reported that glomeruli and renal platelet-activating factor (PAF) production were increased after renal ischaemia. So, we studied the possible relationship between ET and glomeruli or renal PAF production in post-ischaemic acute renal failure.5. Glomeruli from ischaemic rats produced greater amounts of PAF than glomeruli from normal or anti-ET antibody-treated ischaemic rats. In addition, total renal PAF production was higher in ischaemic-untreated than in non-ischaemic or anti-ET-treated rats. Glomeruli incubated with 10-7 M-endothelin produced much more PAF than those incubated in control conditions (138-4 + 10-5 vs. 80-2 +9-4 pg PAF (mg protein) 1; means +S. E. M.; n = 10).6. In conclusion, the present study suggests that endothelin plays a role in the persistent renal vasoconstriction that characterizes post-ischaemic acute renal failure. In addition, the observed increase in glomerular PAF production after renal ischaemia may be due to the action of endothelin.

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