M. Cacciari

Urinary prostanoid excretion in healthy women with different degrees of induced potassium depletion.

Plasma renin activity (PRA), urinary excretions of PGE2, 6-keto-PGF1 alpha (6KPGF), TXB2 and renal function were determined in healthy women both in normal potassium balance (N, n = 14) and in experimental potassium depletion (KD). KD was induced by natriuretic treatment--associated to replacement of net NaCl and water losses--in the presence of either normal (congruent to 50 mmol/d) or low (less than or equal to 10 mmol/d) dietary potassium intake. By using different depletive patterns, three groups with estimated cumulative potassium deficit (mean +/- SEM) of 124 +/- 38 (KD0, n = 8), 160 +/- 43 (KD1, n = 8) and 198 +/- 22 mmol (KD2, n = 6), respectively, were obtained. Renal function by the clearance (cl.) method and urinary prostanoid concentrations by the RIA method were estimated during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis induced by a low-dose infusion of lysine-8-vasopressin. 1. In KD0 group the potassium depletive treatment was inefficacious in significantly reducing either the plasma potassium concentration (PK) or the urinary potassium excretion (UKV). The reductions of PK and UKV as well as the enhancement of PRA became significant in KD1 and KD2 groups. 2. The urinary prostanoid excretions were not significantly changed in the KD0 and KD1 groups while in the KD2 group they were reduced, mainly concerning the urinary 6KPGF excretion. 3. Furthermore in the KD2 group, with larger potassium depletion, some of the typical hypokalemic renal dysfunctions appeared. The data suggest that a pathophysiologically critical degree of potassium depletion is associated with an inhibited renal prostanoid synthesis as well as an increased renin secretion.

Effects of experimental salt depletion on urinary prostanoid excretions in normal women

The effects of moderate salt depletion on urinary excretions of prostanoids (PG)E2, 6-keto-PGF1alpha (6KPGF) and thromboxane (TX)B2 have been investigated in healthy women (SD group, n = 14). Salt depletion was obtained by combining a low sodium chloride dietary intake (< 60 mmol per day) with natriuretic and potassium sparing treatment. At the end of the treatment, the cumulative sodium deficit was 438 +/- 42 mmol (mean +/- SEM). Plasma renin activity (PRA) and urinary aldosterone excretion were determined in basal conditions. Renal functional exploration was performed during hypotonic polyuria (by oral water load) and subsequent moderate antidiuresis (by low dose infusion of an antidiuretic hormone analogue). In both phases, renal function was estimated by the clearance (cl.) method and the urinary concentrations of PGE2, 6KPGF and TXB2 by RIA method. The control group was composed of 20 healthy women in normal sodium and potassium balance (N group). Salt depletion was effective in increasing the basal values of plasma renin activity (PRA) and urinary aldosterone excretion. Moreover, it was effective in inducing the following during polyuria: (a) a depression of the diuretic response to water load in presence of a reduction in plasma osmolality; (b) a reduction in creatinine cl. in the absence of significant changes in mean arterial pressure; (c) an increase in the fractional reabsorption of sodium and chloride, in particular at the level of the diluting segments. Both in polyuria and in antidiuresis, the excretions of 6KPGF and TXB2 were higher in the SD vs. N group, while the excretion of PGE2 was not significantly different. In SD and N pooled groups, significant positive correlations were shown between basal PRA and urinary excretions during polyuria of 6KGPF and TXB2, (but not of PGE2) as well as between the excretions of the two metabolites. In conclusion, functionally effective salt depletion induces in healthy women a stimulation of renal synthesis of both prostacyclin and thromboxane. The excretory data do not give evidence of a similar effect on PGE2 synthesis.

Antagonistic effects of sulpiride ―racemic and enantiomers- on renal response to low-dose dopamine infusion in normal women

In healthy women during moderate hydrosaline retention we have evaluated the antagonistic effects of sulpiride--enantiomers and racemic--on the renal action of a low-dose dopamine (DA) infusion (0.1 microgram/kg/min). The studies were performed, in hypotonic polyuria, by the clearance (C1) method in (1) hydrosaline retention (n = 23), (2) retention + dl-sulpiride (n = 8), (3) retention + d-sulpiride and (4) retention + l-sulpiride (in the latter two cases n = 7 subjects submitted to paired studies). Hydrosaline retention was induced by deoxycorticosterone acetate treatment. A common pattern of sulpiride treatment was applied. The DA renal hyperemia is abolished by l-sulpiride while it is transitorily attenuated by d-sulpiride. In both conditions 3 and 4 the increase in glomerular filtration rate, the inhibition of fractional isosmotic sodium reabsorption and the increase in urinary sodium excretion--induced by DA in condition 1--are suppressed. On the contrary, DA inhibition of fractional anisosmotic sodium reabsorption is not affected by sulpiride. The data indicate that DA renal hyperemia results from the action of DA on DA2 receptors; the DA inhibition of sodium transport by the diluting segments does not appear to be mediated by typical DA receptors.

Interactions between the renin-angiotensin system and prostanoids in modulating renal function in potassium-depleted healthy women

Plasma renin activity (PRA) and urinary aldosterone excretion were determined in healthy women with normal potassium balance (N, n = 20) or experimental potassium depletion (KD). KD was induced by natriuretic treatment--associated with replacement of net NaCl and water losses--and low dietary potassium intake (< or = 10 mmol/d). By using different depletion patterns, three groups were obtained with cumulative potassium deficits (mean +/- SEM) of 160 +/- 43 (KD1, n = 8), 198 +/- 22 (KD2, n = 6) and 215 +/- 54 mmol (KD3, n = 6). The renal function by the clearance (cl.) method and urinary concentrations of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha (6KPGF), and thromboxane B2 (TXB2) by the RIA method were estimated during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis induced by low-dose infusion of lysine-8-vasopressin (LVP). 1. In all KD groups the depletion treatment significantly reduced both potassium plasma concentration (PK) and urinary potassium excretion while it increased basal PRA; the basal urinary aldosterone excretion was not significantly different from normokalemic controls. In the KD3 vs KD1 group the P kappa value was significantly lower. 2. In both KD2 and KD3 groups as compared to the N group, several hypokalemic-like renal dysfunctions--absent in the KD1 group--occurred. Particularly, in the KD2 + KD3 vs N group the renal ability in both urine diluting (water load) and concentrating (LVP infusion) was significantly impaired.(ABSTRACT TRUNCATED AT 250 WORDS)