No abstract

Mineralocorticoid receptors (MRs) expressed in limbic neurons, notably of hippocampus, retain both aldosterone and corticosterone. Basal concentrations of corticosterone already substantially occupy the limbic MR type, suggesting that in hippocampal neurons, MR activity rather than ligand bioavailability is rate limiting. The periventricular region expresses MRs involved in the control of salt homeostasis, which are aldosterone selective because of the presence of 11beta-hydroxysteroid dehydrogenase. MR is in hippocampal CA1, CA2, and dentate gyrus colocalized with glucocorticoid receptors (GRs). Both receptor types mediate in a coordinate manner the corticosterone action on information processing critical for behavioral adaptation and associated neuroendocrine responses to stress. MRs operate in proactive mode determining the sensitivity of the stress response system, while GRs facilitate recovery from stress in reactive mode. On the neuronal level, MR-mediated action maintains a stable excitatory tone and attenuates the influence of modulatory signals. In contrast, GR-mediated effects suppress excitability transiently raised by excitatory stimuli. MR is also involved in control of autonomic outflow and volume regulation. This was demonstrated by the effect of an MR antagonist, which was administered centrally, because mdr P-glycoproteins hamper the access of synthetic steroids to the brain. The MR antagonist attenuates pressor responses to a stressor, such as experienced during tail sphygmography. Diuresis and urinary electrolyte excretion are increased after the MR antagonist, but this effect is abolished after bilateral denervation of the kidney. It is presently unknown in which brain cells the MR-mediated effects on these aspects of central cardiovascular regulation occur.

No abstract

The neurohypophysial hormone vasopressin exerts antidiuretic, vasopressor and behavioural effects (for example, facilitation of memory processes). Vasopressin may alter animal behaviour via direct effect on brain processes. Recently, however, it has been suggested that vasopressin acts mainly at peripheral receptor systems and influences behavioural mechanisms by altering visceral afferent signals. We now present data showing that (1) central administration of [Arg8]vasopressin (AVP) and more potently [pGlu, Cyt]AVP(4-8), the desglycinamide derivative of a peptide generated from AVP by brain synaptic membranes, produce the behavioural effect (promotion of passive avoidance behaviour) without the pressor effect; (2) central administration of a vasopressor antagonist blocks the behavioural but not the pressor effect of systemically administered AVP; and (3) [pGlu, Cyt]AVP(4-8) induces the behavioural effect in the absence of the pressor effect. The results indicate that AVP and related peptides affect passive avoidance behaviour by a direct central action and that the structural requirement for activation of central vasopressin receptors differs from that of the peripheral cardiovascular receptors, although both can be blocked by the same vasopressor antagonist.

The urinary excretion of kallikrein, an enzyme which cleaves a vasodilator kinin from kininogen substrate, was examined in three types of hypertensive rats. Enzyme activity was measured by both esterase activity (isotopic assay) and bioassay with purified rat urinary kallikrein as a standard. Excretion of kallikrein was found to increase with age in spontaneously hypertensive rats, but levels were lower and stable in normotensive Wistar control animals. Rats with desoxycorticosterone-salt hypertension excreted markedly more, whereas rats with renal hypertension excreted significantly less kallikrein than did control animals. The alterations in kallikrein excretion were unrelated to changes in urine volume and protein excretion. The findings indicate that the kallikrein-kinin system may be involved in different forms of hypertension in the rat.