Interaction of circulating hormones with the brain: the roles of the subfornical organ and the organum vasculosum of the lamina terminalis.

1. Most circulating peptide hormones are excluded from much of the brain by the blood-brain barrier. However, they do have access to the circumventricular organs (CVO), which lack the blood-brain barrier. Three of the CVO, the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT) and area postrema, contain neurons responsive to peptides such as angiotensin II (AngII), atrial natriuretic peptide and relaxin. 2. We have studied the patterns of neuronal activation, as shown by Fos expression, in the SFO and OVLT in response to systemically infused AngII, relaxin or hypertonic saline and have found subgroups of neurons activated by the different stimuli. 3. Systemic infusion of relaxin or hypertonic saline activated neurons almost exclusively in the outer regions of the SFO and in the dorsal cap of the OVLT. Many of these neurons send axonal projections to regions of the brain subserving vasopressin secretion and thirst, such as the median preoptic, supraoptic and hypothalamic paraventricular nuclei. 4. At moderate blood concentrations, AngII only stimulates neurons in the inner core of the SFO and lateral regions of the OVLT. Higher levels of AngII in the bloodstream activate additional neurons in the outer parts of the SFO that connect to the supraoptic, paraventricular and median preoptic nuclei and these probably mediate water drinking and vasopressin secretion induced by blood-borne AngII. The efferent connections and the functions mediated by angiotensin-sensitive neurons in the inner core of the SFO and lateral part of the OVLT are unknown.