Effects of aldosterone on intralymphocytic sodium and potassium in patients with primary aldosteronism

Abstract

In vitro effects of aldosterone have been described with regard to the intracellular sodium and potassium concentrations of human mononuclear leukocytes. In the present paper the in vitro effect of aldosterone on the intracellular sodium and potassium of human mononuclear leukocytes in 6 patients with primary aldosteronism was investigated. Except for one patient with elevated intracellular electrolytes, sodium and potassium in mononuclear leukocytes of patients with aldosteronism without incubation were within the range for normals. In the patients, no significant change of intracellular sodium or potassium was observed during incubation with or without aldosterone (1.4 nmol/l), whereas in normals, the loss of sodium and potassium during incubation without aldosterone was prevented by 1.4 nmol/l aldosterone. This insensitivity to aldosterone indicates that intracellular electrolytes in mononuclear leukocytes of patients with primary aldosteronism are kept in normal ranges by mechanism which are independent of mineralocorticoids and may represent the cellular correlate to the renal 'escape' phenomenon in aldosteronism.Recently, mineralocorticoid receptors and effects of aldosterone on intracellular (ic) sodium and potassium have been described for human mononuclear leukocytes (HML) (Armanini et al. 1985a;Wehling et al. 1987). The use of HML appears to provide an easily accessible model for studying the possible physiological effects of aldosterone bind¬ ing to type I receptors with regard to ic electro¬ lytes in vitro.The clinical significance of these receptors was underlined by the demonstration of absent or a decreased number of mineralocorticoid receptors and the lack of electrolyte response to aldosterone in HML of patients with pseudohypoaldosteronism (Armanini et al. 1985b; Wehlingetal. 1986).For patients with primary and secondary aldo¬ steronism, a reduced number of mineralocorti¬ coid receptors has been shown on HML (Armani¬ ni et al. 1987), thus indicating a 'down-regulation' in response to chronically elevated serum levels of aldosterone. It was hypothesized that this downregulation contributes to the 'escape' not only of HML, but also of renal tubular cells, from mine¬ ralocorticoid effects which opposes the develop¬ ment of more severe sodium retention and hypokalaemia in these patients. To further study the physiological implications of these findings at the cellular level, the miner¬ alocorticoid effector mechanism was investigated in HML of patients with primary aldosteronism. Patients and MethodsPatients Six patients with primary aldosteronism (4 males, 2 females; mean age ± SD 50.5 ± 7.6 years) were studied. Important clinical data and laboratory findings are summarized in Table 1. The diagnosis was suspected because of mild hypertension, mild hypokalaemia, elev-

Inheritance of Mineralocorticoid Effector Abnormalities of Human Mononuclear Leucocytes in Families With Pseudohypoaldosteronism

“…High-affinity aldosterone binding sites have been described not only in classical target tissues such as kidney tubules but also in other tissues such as hippocampus (Krozowski & Funder, 1983), mammary gland (Quirk et al, 1983), endothelial cells (Meyer & Nicols, 1981) and, recently, human mononuclear leucocytes (HML, Armanini et al, 1985b). Additionally, a mineralocorticoid (MC) effector mechanism was demonstrated in these cells (Wehling et al, 1987a): aldosterone concordantly increases both the sodium and potassium concentrations of HML.…”

“…The concordant movement of Na+ and K+ by MC appears to be the result of both the increased Na+ permeability of the plasma membranes (Bohr et al, 1984), and events secondary to this, e.g. a subsequent activation of the Na+, K+-ATPase (for more detailed discussion see Wehling et al, 1987a). It is notable that there is a precedent for a unidirectional effect of MC on Na+ and K+ in studies of DOCA-hypertensive rats in which an increase of both intralymphocytic Na+ and K+ was observed in response to DOCA (Myers & Bohr, 1985).…”

“…The clinical relevance of the model was underlined by the observation of a reduced number of MC receptors and a lack of effects of aldosterone on intracellular electrolytes in HML of patients with primary aldosteronism (Armanini et al, 1987, Wehling et al, 1987b, thus indicating a 'down-regulation' of the receptor and/or effector mechanism in response to chronically elevated serum levels of aldosterone.…”

“…Mineralocorticoid (MC) receptors and the effects of aldosterone on intracellular sodium and potassium have been described for human mononuclear leucocytes (HML) (Arrnanini et al, 1985b;Wehling et al, 1987a). In these cells, intracellular sodium and potassium concentrations decrease during incubation without aldosterone, but remain constant in the presence of aldosterone.…”

Extrarenal receptor-effector-mechanisms for aldosterone: The sequence of effects on the cellular electrolyte transport in human lymphocytes and their implications for disorders of the water and electrolyte balances

“…Except for one patient with elevated intracellular electrolytes, sodium and potassium in non-incubated mononuclear leukocytes of patients with aldosteronism were within the range for normals. For the patients no significant change of intracel¬ lular sodium or potassium was observed during in¬ cubation with or without aldosterone (1.4 nmol/1), whereas in normals the loss of sodium and potas¬ sium during incubation without aldosterone was prevented by 1.4 nmol/1 aldosterone (56). This insensitivity to aldosterone indicates that intracellular electrolytes in mononuclear leukocytes of patients with primary aldosteronism are kept within normal ranges by mechanisms independent of mineralocorticoids and may represent the cellular correlate of the renal "escape" phenomenon in aldosteron¬ ism.…”