Endothelin-A blockade attenuates systemic and renal hemodynamic effects of L-NAME in humans.

Eight Na-repleted volunteers underwent 3 separate 90-minute infusions of either N(G)-nitro-L-arginine methyl ester (L-NAME) 3.0 mg. kg(-1). min(-1) or endothelin-A receptor (ET-A) blocker BQ-123 (BQ) 0.125 nmol. kg(-1). min(-1) or both. Mean arterial pressure (MAP), glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistances (RVR), and sodium excretion rate (UNaV) were measured at baseline (b) and from 0 to 45 minutes (period 1) and 45 to 90 minutes (period 2) of infusion. BQ alone had no effect. GFR declined by 4.9% (P<0.001 versus b) in period 1, to 9.9% (P<0. 001) in period 2 with L-NAME, and by 3.3% (P<0.01) to 6.6% (P<0.001) with L-NAME plus BQ (P=NS between L-NAME and L-NAME plus BQ). UNaV fell equally with L-NAME or L-NAME plus BQ. MAP rose significantly in period 2 with L-NAME (6.9%; P<0.001) but not with coinfused BQ (2. 1%; P=NA versus b, P=0.005 versus L-NAME alone). RBF declined by 12. 2% (P<0.001) to 18.3% (P<0.001) with L-NAME and by 4.6% (P<0.005) to 8.2% (P<0.001) with L-NAME plus BQ. These changes were smaller with L-NAME plus BQ (P<0.05 in period 1 and P<0.02 in period 2). Blunted changes were also seen for RVR (P<0.005 in period 1 and P<0.001 in period 2 between L-NAME alone and L-NAME plus BQ). These findings show that systemic and renal vasoconstriction due to L-NAME are attenuated by BQ, which suggests that an interaction between endogenous nitric oxide production and ET-A activity participates in the maintenance of baseline systemic and renal vascular tone in humans.

Dopamine-2 receptor blockade potentiates the renal effects of nitric oxide inhibition in humans.

In eight young healthy subjects on a 240 mM Na diet mean arterial pressure (MAP), renal hemodynamics and renal handling of Na and exogenous Li were measured at baseline and during acute nitric oxide (NO) inhibition with 90-minute infusion of 3.0 microg/kg x min(-1) of N(G)-L-arginine methyl ester (L-NAME). The same experiment was repeated with infusion of 50 microg/kg x min(-1) of DA2 receptor blocker L-Sulpiride (L-SULP) alone and, finally, with simultaneous infusion of both L-NAME and L-SULP. L-SULP alone did not elicit any effect. L-NAME alone produced no changes in MAP from 0 to 45 minutes (P1) and a 6.6% increase at 45 to 90 minutes (P2) of infusion. Effective renal plasma flow (ERPF, PAH clearance) and glomerular filtration rate (GFR, inulin clearance) declined by 10.2% and 7.6%, respectively, in P1 and by 15.3% and 11.5% in P2. Filtration Fraction (FF) rose by 4.2% in P2. Calculated renal vascular resistance (RVR) increased by 13.0% to 25.6%. Fractional excretion of Na (FENa) and Li (FELi) fell by 20.0% and by 16.0%, respectively, in P1 and by 40.0% and 25.1% in P2. All these variations, except for MAP and GFR, were significantly greater during coinfusion of L-NAME and L-SULP. ERPF declined by 17.8% to 33.7%, FENa by 26.7% to 53.3%, FELi by 13.8% to 34.8%, while RVR rose by 22.5% to 59.1% and FF by 10.1% to 29.3%. The present data confirm that NO blockade with low-dose systemic infusion of L-NAME produces renal vasoconstriction, reduced GFR with slight increase in FF, and enhanced tubular Li, and Na reabsorption. Since increase in RVR and FF and decrease in FENa and FELi are markedly potentiated by the simultaneous infusion of DA2 blocker L-SULP, which exerts no effects by itself, we suggest that DA interactions between DA system at the level of DA2 receptors and basal NO production play a physiological role in the regulation of renal function in humans.

Angiotensin II blockade does not prevent renal effects of L-NAME in sodium-repleted humans.

In seven healthy, young subjects on a 240 mmol sodium diet, mean arterial pressure (MAP), renal hemodynamics, and renal handling of Na and exogenous Li were measured at baseline and during short-term nitric oxide (NO) blockade with a 90-minute infusion of 3.0 microg x kg(-1) x min(-1) of N(G)-L-arginine methyl ester (L-NAME). The infusion was performed twice: after a 3-day pretreatment with either placebo or 50 mg losartan to block Ang II receptors. With placebo, L-NAME produced no change in MAP from 0 to 45 minutes (period 1) and only a 5% increase at 45 to 90 minutes (period 2) of infusion. Effective renal plasma flow (ERPF, PAH clearance) and glomerular filtration rate (GFR, inulin clearance) declined by 11.7% and 8.0%, respectively in period 1 and by 14.6% and 11.6%, respectively, in period 2. Calculated renal vascular resistance (RVR) increased by 13.0% to 20.6%. Fractional excretion of Na (FE(Na)) and Li (FE(Li)) fell by 30.0% and 21.0%, respectively, in period 1 and by 44.2% and 31.1% in period 2. All these variations were significant versus baseline. With losartan, the rise in MAP at 45 to 90 minutes was completely abolished, whereas all changes in ERPF, GFR, RVR, FE(Na), and FE(Li) in response to L-NAME were the same as those observed with placebo. The present data show that NO blockade with low-dose systemic infusion of L-NAME produces renal vasoconstriction, reduced GFR, and increased tubular Na reabsorption independent of changes in MAP. Reduced FE(Li) indicates an effect of NO on the proximal tubule. Since these changes are not prevented by losartan, we conclude that in Na-repleted humans, renal vasoconstriction and Na-retaining effects of inhibition of basal NO production are not due to the unopposed action of endogenous Ang II.

Role of blood pressure in the natriuretic response to acute calcium channel blockade in humans.

Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and renal excretion of sodium and lithium were measured before and after acute oral administration of 20 mg nifedipine in 19 essential hypertensive patients. In 10 of them, with a diastolic pressure less than 105 mm Hg, nifedipine resulted in a decrease in mean blood pressure toward normal (109 +/- 2 to 97 +/- 2, p less than 0.001), a 27% increase in ERPF (p less than 0.001), no change in GFR, and an increase in fractional sodium excretion (28%, p less than 0.001). In nine subjects with a diastolic pressure greater than or equal to 105 mm Hg, nifedipine produced a decrease in mean blood pressure (133 +/- 6 to 117 +/- 4, p less than 0.001), which however remained higher than in mild hypertensives (p less than 0.001). ERPF rose by 29% (p less than 0.001), GFR remained unchanged, and fractional sodium excretion definitely increased more than in mild hypertensives (126%, p less than 0.001), as did fractional lithium excretion, used as an estimate of proximal tubular sodium handling. Acute nifedipine produces renal vasodilation in hypertensives, but with a greater natriuretic response in those subjects whose blood pressure remains elevated. Thus, acute natriuresis following nifedipine administration is largely dependent on the interaction between changes in arterial pressure and renal hemodynamics.

[Lyell's syndrome: study of a clinical case]. / Sindrome di Lyell: considerzioni su di un caso clinico.

The Authors report a case of Lyell's syndrome. Previous administration of sulfadossine was identified as the precipitating cause of the syndrome. The clinical history and the treatment of the case are described. Two aspects of the latter were considered to be particularly important: a careful control of the hydroelectrolytic balance and positive action to favour the rapid re-epithelialization of the cutaneous area affected.

[Na/K transport in red blood cells from normal subjects: methodological problems (author's transl)]. / Transporto Na/K nei globuli rossi di soggetti sani: problemi metodologici.

In this work we present a method which evaluates the facility of applying and reproducing ion fluxes in human cells using radioactive 22Na as a tracer. Intracellular sodium concentration, rate constants for total (oKNa TOT), ouabain-sensitive (oKNa OUABs) and ouabain-insensitive (oKNa OUABins), sodium efflux and relative effluxes obtained by multiplying the rate constant by the sodium concentration were measured in the red cells of 20 normal subjects. Our results have been shown to be comparable with those obtained in other reports and show a statistically significant relationship between intracellular sodium concentration and the rate constant for active sodium efflux: one would conclude that the intracellular sodium constant probably depends on the activity of the sodium pump genetically determined in each individual. Since such a method is precise can be exactly reproduced, it can be applied to the study of cellular metabolism of different clinical disorders characterized by significant fluid and electrolyte imbalances.

[Na/K transport in red blood cells from severely burned patients (author's transl)]. / Transporto Na/K nei globuli rossi di soggetti con gravi ustioni.

The working of the Na/K pump in the red cells of 6 patients with extensive burns was analyzed using radioactive substances with the aim of comparing their red cells with those of 20 normal subjects. In the red cells of patients with extensive burns was found that the intracellular sodium concentration was clearly increased, that the rate constant of ouabain-sensitive efflux diminished, and that the total sodium efflux was augmented by the increase of the ouabain-insensitive part. It is likely that the intra and extra-cellular transportation defects produce an accumulation of sodium inside the cell which succeeds in stimulating the activity of the pump. Although this pump is impaired, the high sodium concentration obtains a new steady state characterized by apparently normal ouabain-sensitive sodium efflux and by an increased ouabain insensitive efflux. The pathogenesis of these defects of cellular homeostasis which are linked to the presence of various complex mechanisms (shock, calorie balance, fluid and electrolyte imbalances, the circulation of "toxic substances" etc), in cases of extensive burns, has not been completely elucidated.

Observations on lipid metabolism in chronic renal failure, during conservative and haemodialysis therapy.

The main variables of glycolipid metabolism (blood non-esterified fatty acids, triglycerides, cholesterol, insulin, glucose) have been measured in basal conditions in uraemic patients on conservative treatment and on dialysis of different duration and bath glucose concentration (no glucose, 1 g/l, 2 g/l). Basal values for the patients on conservative dietary treatment are not different from normal. In dialysed patients, the blood non-esterified fatty acid and triglyceride concentrations are increased (p less than 0.001) while cholesterol glucose and insulin levels are unchanged. No significant difference is found between the various types of dialysis, having different duration and bath glucose concentration

[Acid-base modifications induced by treatment with concentration-reinfusion of ascitis fluid in cyrrhosis (author's transl)]. / Modificazioni dell'equilibrio acido-base indotte dal trattamento di estrazione-concentrazione-reinfusione del liquido ascitico nella cirrosi epatica

In 9 cyrrhotic patients with ascites we have studied the acid base status and the renal acidogenic capacity (urinary titrable acidity, ammonia) before, during and after reinfusion of concentrated ascitic fluid. Acid-base parameters have been evaluated also in the ascitic fluid and in the concentrated reinfusion fluid. The treatment does not determine any significant variation of acid base equilibrium in the cyrrhotic patients, while there is a remarkable loosing of CO2 with lowering of pCO2 in the concentrated ascitic fluid. We discuss the main physiopathological factors involved in such a type of treatment.