Maurice Abramow

Natriuresis and atrial natriuretic factor secretion during inappropriate antidiuresis.

The mechanisms responsible for the natriuresis encountered in the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are not fully understood. The present study explores the role of atrial natriuretic factor (ANF). Eight subjects unable to excrete ingested free water normally (three patients with SIADH and five healthy humans after intranasal administration of desmopressin) underwent a standard oral water loading test. Plasma ANF level and urinary sodium excretion increased during water retention, whereas plasma aldosterone value decreased later. The increment of urinary sodium excretion rate was significantly correlated with that of plasma ANF. In two patients with hyponatremia due to SIADH, plasma ANF levels were increased during the hyponatremic phase of their condition and decreased under water restriction. In one of them, marked natriuresis was observed when the plasma ANF level was high. It is concluded that secretion of ANF is acutely and chronically stimulated during water retention in SIADH and that ANF may be in part responsible for the natriuresis encountered in inappropriate antidiuresis.

Inhibition by lithium of the hydroosmotic action of vasopressin in the isolated perfused cortical collecting tubule of the rabbit.

Because treatment with lithium salts may impair renal concentrating ability, we investigated the possibility of a direct effect of lithium ions on the permeability to water of the collecting duct epithelium. The coefficient of hydraulic conductivity (Lp) of isolated perfused rabbit cortical collecting tubules (CCT) was measured in the presence and absence of arginine-8-vasopressin (AVP), or 8-bromo (Br) cyclic AMP (cAMP) and/or lithium chloride (Li 10 mM). In the absence of AVP, Li in the lumen for 30 min failed to affect basal water permeability; however, in tubules preincubated with Li in the lumen for 80 min, basal water permeability was reduced to 30% of the value found in control tubules (P less than 0.01). In CCT incubated at 25 degrees C with Li in the lumen for 3 h, the hydroosmotic response to 2.5 microU X ml-1 AVP (Lp = 6.88 +/- 1.54 nl X cm-2 X s-1 X atm-1) was significantly lower than that in the control tubules (13.98 +/- 1.59, P less than 0.01); the inhibition was not reversible. When Li was present in the peritubular medium only, the hydroosmotic effect of AVP was not different from that of the controls. The hydroosmotic effect of 25 microU/ml AVP was investigated at 37 degrees C. CCT exposed to Li in the lumen had a 49% inhibition of peak Lp under AVP (Lp = 10.98 +/- 1.17) as compared with control tubules (Lp = 21.39 +/- 1.51; P less than 0.005). In contrast, the hydroosmotic response to 8-Br-cAMP was not affected by lithium. The results are compatible with the view that Li inhibits the action of AVP at the level of the regulating protein or the catalytic unit of the membrane adenylate cyclase and that the site of the interaction can be reached by lithium only from the cytoplasmic side. The Li-antidiuretic hormone (ADH) interaction found here may represent the earliest pathophysiological event underlying the renal concentrating defect observed after Li administration.

Subtypes of Madin-Darby canine kidney (MDCK) cells defined by immunocytochemistry: Further evidence for properties of renal collecting duct cells

The Madin-Darby canine kidney (MDCK) cell line has been proposed as a model for studying intercalated (IC) cells of the renal cortical collecting duct. The IC cells are characterized by peanut lectin (PNA) binding capacity, carbonic anhydrase (CA) activity and Cl-−HCO3-exchange mediated by a band 3-related protein. It has been suggested that these properties are also expressed in MDCK cells. So far however, the nature of the specific protein involved in Cl-−HCO3-exchange, the type of CA isozyme and the relationship between these two characteristics and PNA binding, have not been investigated in MDCK cells by immunocytochemical methods. Using two antibodies raised against human erythrocyte band 3 protein and two against human erythrocyte CA I and II isozymes, our study provides evidence that a protein related to band 3 is expressed in about 5% of cultured MDCK cells; these band 3-positive cells do not bind PNA and are not reactive for CAI or CAII. About 30% of the MDCK cells bind PNA, two-thirds of which are also CAII-positive. A majority (about 65%) of MDCK cells is not reactive for the three markers used; their density is increased after incubation with aldosterone. These data indicate (i) that the Cl-−HCO3-exchanger of the MDCK cells could be related to human erythrocyte band 3, (ii) that the CA activity of the MDCK cell line bears antigenic identity with the erythrocyte CA II isozyme and (iii) that the latter is always co-localized with PNA binding. These results provide immunocytochemical evidence for the heterogeneity of the MDCK cell line, which might reflect the cellular heterogeneity encountered in the renal cortical collecting duct. Our data also indicate that clonal selection will be required for future functional studies of the MDCK cells.

Impaired hydroosmotic response to vasopressin of cortical collecting tubules from lithium-treated rabbits

The hydroosmotic action of [arginine]vasopressin (vasopressin, 25 μU/ml) and of 8-Br-cAMP (10−4 M) was studied in vitro in perfused cortical collecting tubules (CCT) isolated from rabbits fed with lithium chloride for 3 weeks. Vasopressin-dependent water reabsorption was significantly inhibited by 65% although no lithium was used in the in vitro experiments. The hydroosmotic action of 8-Br-cAMP was also inhibited by previous Li treatment, but the effect was smaller in magnitude. Water intake, diuresis, and urinary osmolality were no different in the lithium-treated animals as compared with respective pretreatment values or with control animals given an equivalent amount of sodium chloride. Neither the creatinine clearance nor the maximal urinary concentrating ability were modified by lithium treatment. A mathematical model simulating water reabsorption along the CCT predicts that a 65% reduction of vasopressin-stimulated hydraulic conductivity, as observed in the Li group, may not be sufficient to prevent a complete osmotic equilibration at the end of the CCT in vivo. We conclude that: (a) in the rabbit, lithium administration induces an impairment of the hydroosmotic action of vasopressin in the CCT, which is due to an inhibition of pre- and post-cAMP events, (b) The inhibition of vasopressin action can be demonstrated in vitro at a time when no detectable impairment of the water conservation process occurs in vivo.