Brain mineralocorticoid receptor function.
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Animals↗
Biomedical subjects
D T van den Berg
Publications and source records attributed to D T van den Berg.
Brain mineralocorticoid receptor diversity: functional implications.
Mineralocorticoid receptors (MRs) in neurons of the anterior hypothalamus and the periventricular brain regions mediate aldosterone-selective actions on sodium homeostasis, salt appetite and cardiovascular regulation. Corticosterone is not effective in these neurons, possibly because it is enzymatically inactivated. However, MRs in limbic brain regions, notably in the hippocampal neurons, do already respond to very low concentrations of both corticosterone and aldosterone. The MR-mediated effects stabilize neuronal transmission and appear critical for neuronal integrity of a sub-region of the hippocampus: the dentate gyrus. Higher concentrations of corticosterone induced by stress and the circadian rise progressively activate the lower affinity glucocorticoid receptors (GRs), which in coordination with MR-mediated actions then facilitate adaptive processes required for recovery of homeostasis. It is postulated that this balanced MR- and GR-mediated action of corticosterone is of critical importance for regulation of the stress response and behavioural adaptation.
Aldosterone↗
Differential central effects of mineralocorticoid and glucocorticoid agonists and antagonists on blood pressure.
Systolic blood pressure was measured, using an indirect tail method, in conscious male rats at several time intervals after the intracerebroventricular injection of mineralo-and glucocorticoid agonists and antagonists. Intracerebroventricular administration of the antimineralocorticoid RU 28318 (10 ng) decreased blood pressure, while the antiglucocorticoid RU 38486 (10 ng) caused an increase, which was slower in onset and of longer duration. The effect of the antimineralocorticoid was maximal at 8 h and had disappeared after 24 h. The antiglucocorticoid had a significant effect 24 and 48 h after injection. Neither antagonist was effective when administered sc at the same dose (10 ng). Intracerebroventricular administration of aldosterone (10 ng) and the selective glucocorticoid agonist RU 28362 (10 ng) increased and decreased blood pressure, respectively. Corticosterone given intracerebroventricularly (10-100 ng) did not affect blood pressure unless the dose was increased to 1 microgram. Two weeks after adrenalectomy a decrease in blood pressure was observed when the rats were given 0.9% saline instead of water to drink. Replacement therapy with corticosterone (12.5-mg steroid pellet, sc) restored blood pressure to the level in the sham-operated controls. The chronically elevated level of circulating corticosterone produced by a 100-mg sc corticosterone pellet increased blood pressure. The 12.5-and 100-mg sc corticosterone pellets resulted in plasma corticosterone levels of approximately 3 and 20 micrograms/100 ml, respectively. Intracerebroventricular administration of the glucocorticoid and mineralocorticoid antagonists (10 ng) increased and decreased, respectively, the blood pressure of the adrenalectomized rats receiving corticosterone substitution. From these data we conclude that corticosteroids can affect the central regulation of blood pressure. The mineralo- and glucocorticoids have opposite effects, which differ in onset and duration. The mineralocorticoids increased blood pressure, whereas the glucocorticoid decreased it.
Adrenalectomy↗
Brain corticosteroid receptors and regulation of arterial blood pressure.
A single intracerebroventricular injection of 10 ng of the mineralocorticoid aldosterone in normotensive male Wistar rats induced a transient increase in blood pressure. Corticosterone produced this response only at a 100-fold higher dose. In contrast, a decrease in systolic blood pressure occurred following the intracerebroventricular administration of a selective glucocorticoid agonist (Ru 28362; 10 ng). The intracerebroventricular administration in normotensive and adrenalectomized, corticosterone-replaced, male rats of an antimineralocorticoid (Ru 28318; 10 ng) decreased systolic blood pressure, while an antiglucocorticoid (Ru 38486; 10 ng) caused an increase. These data suggest that adrenal steroids affect central mechanisms underlying cardiovascular regulation by binding to central mineralo- and glucocorticoid receptors.
Animals↗