Estrogens contribute to a sex difference in plasma potassium concentration: a mechanism for regulation of adrenal angiotensin receptors.

BACKGROUND: The adrenal mineralocorticoid aldosterone promotes sodium (Na(+)) reabsorption and potassium (K(+)) loss from the kidney. Female sex steroids such as estrogen and progesterone are known modulators of the renin-angiotensin-aldosterone system. OBJECTIVE: We conducted studies to determine if there is a sex difference in plasma Na(+) concentration ([Na(+)]) and plasma K(+) concentration ([K(+)]), and if interactions between female sex steroids and aldosterone contribute to a sex difference in these electrolytes. METHODS: Plasma [Na(+)] and [K(-)] were determined in weight-matched male and female Sprague-Dawley rats using an ion-selective electrode system. To assess the sensitivity of males and females to aldosterone, the mineralocorticoid was infused chronically by osmotic minipump. The role of female sex steroids in the regulation of plasma electrolyte concentrations was determined in bilaterally ovariectomized (OVX) female rats treated daily with SC injections of progesterone, 17beta-estradiol (E(2)), or selective estrogen receptor (ER) modulators. The role of plasma [K(+)] in the regulation of adrenal angiotensin II type 1 receptor (AT(1)R) expression was determined by manipulating plasma [K(+)] by varying dietary K(-). Adrenal AT(1)R expression was assessed using a radioligand binding assay. RESULTS: Plasma [Na(-)] was not different between male and female rats, but plasma [K(-)] was reduced in females compared with males (P = 0.003). In aldosterone-infused female rats, plasma [Na(+)] was increased and plasma [K(+)] was reduced further than in male rats infused with aldosterone (both, P = 0.001). In OVX female rats, progesterone reduced plasma [Na(+)] (P = 0.04) but had no effect on plasma [K(+)]. In contrast, E(2) increased plasma [Na(+)] (P = 0.01) and reduced plasma [K(+)] (P = 0.001). Dietary K supplementation in E(2)-treated rats returned plasma [K(+)] and adrenal AT(1)R binding to levels observed in control rats. Both an ERa and ERP agonist decreased plasma [K(+)] and decreased adrenal AT(1)R binding (both, P < 0.01). CONCLUSIONS: In these studies, plasma [K(+)] was reduced in female Sprague-Dawley rats compared with males. The effects of aldosterone on plasma electrolytes were enhanced in females compared with males. E(2) treatment reduced plasma [K(+)] and adrenal AT(1)R binding in OVX rats, and the decrease in plasma [K(+)] contributed to the decrease in adrenal AT(1)R binding. Both ERalpha and ERbeta contributed to the estrogen-induced decrease in plasma [K(+)] and adrenal AT(1)R binding.

Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release.

Apelin, a recently isolated neuropeptide that is expressed in the supraoptic and the paraventricular nuclei, acts on specific receptors located on vasopressinergic neurons. The increased phasic pattern of these neurons facilitates sustained antidiuresis during dehydration or lactation. Here, we investigated whether apelin interacts with arginine vasopressin (AVP) to maintain body fluid homeostasis. We first characterized the predominant molecular forms of endogenous hypothalamic and plasma apelin as corresponding to apelin 13 and, to a lesser extent, to apelin 17. We then demonstrated that, in lactating rats, apelin was colocalized with AVP in supraoptic nucleus magnocellular neurons and given intracerebroventricularly inhibited the phasic electrical activity of AVP neurons. In lactating mice, intracerebroventricular administration of apelin 17 reduced plasma AVP levels and increased diuresis. Moreover, water deprivation, which increases systemic AVP release and causes depletion of hypothalamic AVP stores, decreased plasma apelin concentrations and induced hypothalamic accumulation of the peptide, indicating that AVP and apelin are conversely regulated to facilitate systemic AVP release and suppress diuresis. Opposite effects of AVP and apelin are likely to occur at the hypothalamic level through autocrine modulation of the phasic electrical activity of AVP neurons. Altogether, these data demonstrate that apelin acts as a potent diuretic neuropeptide counteracting AVP actions through inhibition of AVP neuron activity and AVP release. The coexistence of apelin and AVP in magnocellular neurons, their opposite biological effects, and regulation are likely to play a key role for maintaining body fluid homeostasis.