G. Romano

Inhibition of urea tubular reabsorption by PGE1 infusion in man.

We have shown that the inhibition of prostaglandin (PG) synthesis in man decreases the fractional clearance of urea (FCurea). To understand the mechanism(s) by which PG affect the renal handling of urea, 6 normal volunteers were randomly studied in maximal antidiuresis (by water deprivation and by administering 1-desamino-8-D-arginine vasopressin) before and during PGE1 infusion, in two separate occasions: (A) after 7 days of normal protein (1 g/kg b.w./day) and water intake (10 ml/kg b.w./day), and (B) after 7 days of low protein intake (0.5 g/kg b.w./day) and high water intake (80 ml/kg b.w./day) to lower the corticomedullary osmotic gradient. During infusion of PGE1 at rates of 0.01, 0.05 and 0.1 micrograms/min/kg, randomly administered, the urinary fluid losses were replaced by infusing equal volumes of hypotonic NaCl (80 mmol/l). To evaluate the time effects of this protocol, control studies were performed in an other 8 subjects receiving vehicle infusion without PGE1. In study A, FCurea rose by 23% (p less than 0.01) at the lowest PGE1 infusion rate (0.01 micrograms/min/kg), in the absence of any simultaneous change in water and salt output, Uosm, PAH and inulin clearance. Higher PGE1 infusion rates (0.05 and 0.1 micrograms/min/kg) were associated with a progressive increase of FCurea (50%, p less than 0.001 and 91%, p less than 0.001, respectively), fractional clearance of water and salt output, inulin and PAH clearance and reduced Uosm from 1,005 (22 SEM; basal value) to 772 (38 SEM; minimum value) mosm/kg (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Effects of Ciclosporin on Renal Hemodynamics and Urinary Protein Excretion in Patients with the Nephrotic Syndrome

The possibility that the renal hemodynamic abnormalities associated with ciclosporin (CS) administration are enhanced in nephrotic patients (NP), leading to severe impairment of renal function and/or to modifications in proteinuria, has not hitherto been tested. Ten NP and 8 healthy subjects (NC) were examined before and after oral CS administration (10 mg/kg body weight in NP and 12 mg/kg body weight in NC: a lower dosage was adopted in NP because of edema overestimating the actual body weight) under water diuresis by standard renal clearance methods. Basal blood volume was lower in NP. Blood CS levels were not significantly different in the two groups. Basal glomerular filtration rate (GFR) was similar in NP and NC, while renal plasma flow (RPF) was lower in NP. After CS, both GFR and RPF significantly decreased in the two groups, but the percent decrease in inulin clearance was greater in NP. Filtration fraction increased only in NC. Basal renal vascular resistances were greater in NP, and significantly increased after CS in both groups. Basal fractional sodium excretion (FENa) was lower in NP: after CS FENa decreased only in NC. Neither plasma renin activity, nor plasma aldosterone changed after CS. When urinary protein excretion (UP) was corrected by GFR, no change was observed after CS; by contrast, selectivity of proteinuria (as assessed by the CIgG/CTransferrin ratio) markedly increased. Our data indicate that CS induces a greater fall in the GFR in hypovolemic NP than in healthy subjects, probably because in the former GFR becomes extremely plasma flow dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Mechanisms of Muzolimine

This study was performed to investigate both the antihypertensive mechanism(s) and the efficacy of Muzolimine, a loop diuretic with no structural similarity to other loop diuretics.

Dopamine (D) Reverses Acute Cyclosporine A (CyA) Nephrotoxicity. Micropuncture Study in the Rat

We have recently shown, by renal micropuncture, that acute CyA-induced nephrotoxicity is entirely due to modifications in glomerular dynamics (1). Several vasodilating drugs have recently been tested in the attempt to prevent or reverse the acute renal dysfunction due to CyA, but, despite some beneficial effects, none of them was able to restore GFR to normal values. This study was carried out to evaluate whether D could counteract the hemodynamic modifications induced by CyA. D, in fact, has a renal vasodilating action if administered at low doses, whichstimulateonly dopaminergic receptors.

Effects of the Loop-Diuretic Muzolimine in Rats with HgCl2 — Induced Acute Renal Failure (ARF)

Pre-treatment with diuretics (D) can prevent the onset or shorten the course of many models of experimental ARF (1). It is not clear, however, whether D can improve renal function when administered after ARF has estabilished. The aim of our study was to investigate the effects of Muzolimine (M) in HgCl2 induced ARF.

Effects of Muzolimine on Experimental Acute Renal Failure (ARF)

Experimental ischemic-ARF has been widely studied because of its pathogenic similarity to human ARF. Administration of loop diuretics immediately after the ischemic insult is of no benefit to renal function (1). This study was carried out to evaluate the effects of a new loop diuretic, Muzolimine (M), active from the peritubular site.