Neuronal effects of neurokinin B on the rat subfornical organ.

The subfornical organ is an essential central nucleus for angiotensin II-induced body fluid regulation. Similar to angiotensin II, centrally injected neurokinin B (NKB) may induce cardiovascular responses by the subfornical organ; however, it does not induce water intake. To clarify this inconsistency, we investigated the neuronal effects of NKB on subfornical organ neurons in slice preparations along with its behavioral effects in vivo. In electrophysiological extracellular recordings, NKB excited angiotensin II-insensitive and inhibited angiotensin II-sensitive neurons. Centrally injected NKB inhibited peripherally injected angiotensin II-induced water intake. These results suggest that NKB-mediated neuronal effects on the subfornical organ are likely to be involved in antidipsogenic responses in addition to the previously reported cardiovascular responses.

Distinct mechanisms underlie the regulation of body fluid balance by neurokinin B and angiotensin II in the rat brain.

Although central injections of either neurokinin B (NKB) or angiotensin II (ANGII) induce a pressor response, they show different involvements in fluid intake behaviors. The aim of the present study was to elucidate the mechanisms by which these two peptides regulate body fluid balance in rats. We demonstrate that intracerebroventricular injections of NKB (1nmol) and ANGII (0.1nmol) both induce pressor responses. However, only ANGII induced significant water intake and increased sodium preference. Co-injection of NKB suppressed the ANGII-induced sodium preference but did not affect the ANGII-induced water intake. Immunohistochemistry for c-Fos, a marker of neuronal activation, revealed that both NKB and ANGII increased neuronal activation in the circumventricular organs and the hypothalamic paraventricular and supraoptic nuclei. In contrast, only ANGII significantly increased c-Fos immunoreactivity in the paraventricular thalamic nucleus, the central amygdala (CeA) and the ventrolateral bed nucleus of the stria terminalis (BSTvl). Co-injection of NKB suppressed the ANGII-induced c-Fos expression in the CeA and BSTvl. These results suggest that centrally injected NKB and ANGII lead to common cardiovascular responses by neuronal pathways through the circumventricular organs and hypothalamus but that they regulate fluid intake behaviors through different pathways. It is likely that the opposing effects of these two peptides on sodium preference can be explained by their differential actions in the CeA and BSTvl, both of which are inhibited by NKB and activated by ANGII.